UK-VARSS UK Veterinary Antibiotic Resistance and Sales Surveillance Report

2015

UK Veterinary Antibiotic Resistance and Sales Surveillance

Editor in Chief

Professor S. Peter Borriello Veterinary Medicines Directorate Woodham Lane New Haw Addlestone Surrey, KT15 3LS

Authors

Veterinary Medicines Directorate  Fraser Broadfoot  Callum Harris  Stacey Brown  Kitty Healey  Katherine Grace  Hannah Reeves

Animal and Plant Health Agency  Chris Teale

Acknowledgements

This report is issued by the Veterinary Medicines Directorate (VMD). Data for the sales section are produced by the VMD. Data for the antibiotic resistance section are produced and collated by the Animal and Plant Health Agency (APHA), the Agri-Food Biosciences Institute (AFBI), and SAC Consulting Veterinary Services (SACCVS). The veterinary antibiotic resistance and sales data monitoring programme is commissioned and funded by the VMD. Data on antibiotic consumption in poultry species were collected by the British Poultry Council and shared with the VMD for publication in this report. Contributions from the Pig Health and Welfare Council and the Cattle Health and Welfare Group were also gratefully received. We would like to thank Steve Eldridge and Elizabeth Marier of the VMD for their help and support with the publication of this report and members of the Defra Antimicrobial Resistance Coordination group (DARC), the Veterinary Products Committee and the APHA Species expert leads for their comments and advice.

Citation

Text and tables may be cited only with the reference to this report: UK-VARSS 2015. UK Veterinary Antibiotic Resistance and Sales Surveillance Report.

Correspondence

Any correspondence relating to this report should be sent by email to: [email protected]

Contents

List of Figures ...... 5

List of Tables ...... 6

Executive Summary ...... 11

Introduction ...... 15

Chapter 1: Sales of Veterinary Antibiotics ...... 17

Chapter 2: Data Collection Activities to determine the level of Antibiotic Usage by Livestock Species ...... 28

Chapter 3: EU Harmonised Monitoring of Antibiotic Resistance ...... 31 Escherichia coli ...... 33

Salmonella spp...... 35

Chapter 4: Clinical Surveillance of Antibiotic Resistance ...... 36 Mastitis Pathogens ...... 37

Respiratory Pathogens ...... 40

Other Animal Pathogens ...... 43

Zoonotic Pathogens ...... 44

References ...... 64

Annexes ...... 67 Annex 1: Changes in Methodology ...... 67

Annex 2: European Population Correction Unit (PCU) ...... 71

Annex 3: Antibiotic Active Ingredients Authorised for Use in Animals ...... 74

Annex 4: Antibiotic Usage Data from British Poultry Council ...... 76

Annex 5: Cascade Prescribing ...... 80

Annex 6: Summary of the EU Harmonised Monitoring Requirements of 2013/652/EU..... 81

Annex 7: Sources of the bacteria to meet the EU Harmonised Monitoring Requirements of 2013/652/EU ...... 82

Annex 8: Disc diffusion breakpoints, corresponding MIC breakpoints and breakpoints under review for the clinical surveillance isolates included in this report ...... 83

Annex 9: Comparison of 2015 ESBL results with those of previous UK surveys ...... 87

Annex 10: EU Harmonised Monitoring, results of Susceptibility testing in Salmonella...... 88

Annex 11: Clinical surveillance data for isolates from bovine mastitis cases ...... 89

Annex 12: Clinical surveillance data for isolates from respiratory infections of cattle, sheep, and pigs ...... 91

Annex 13: Clinical surveillance data for isolates from respiratory infections of pigs ...... 93

Annex 14: Clinical surveillance data for isolates from respiratory infections of sheep ...... 94

Annex 15: ‘Other Veterinary Pathogens’ ...... 96

Annex 16: Clinical surveillance data for E. coli ...... 100

Annex 17: Clinical surveillance data for Salmonella spp...... 115

Annex 18: Data limitations ...... 125

Annex 19: Data sources ...... 128

Annex 20: Glossary of Terms ...... 129

Annex 21: Contributors ...... 132

List of Figures

Figure 1.1: Milligrams (mg) of active ingredient of antibiotic sold for pig and/or poultry only and food producing species per Population Correction Unit (PCU) 2011-2015 ...... 19

Figure 1.2: Milligrams (mg) of active ingredient of “highest priority critically important antibiotics’’ sold for food producing species per Population Correction Unit (PCU) 2011-2015 ...... 20

Figure 1.3: Average annual amount in grams (g) of active ingredient of intramammary antibiotic sold per dairy cow 2011-2015 ...... 21

Figure 1.4: Percentage of active ingredient of antibiotic by class sold for all species in 2015 .... 23

Figure 1.5: Milligrams (mg) of active ingredient of antibiotic by class sold for food producing species per Population Correction Unit (PCU) by class in 2011-2015 ...... 24

Figure 1.6: Percentage of active ingredient of antibiotic sold for all species by route of administration 2011-2015 ...... 27

Figure 3.1: Percentage resistance (interpreted using EUCAST CBPs) in Escherichia coli isolates from pigs (n=150) in 2015 ...... 33

Figure 3.2: Resistance (interpreted using EUCAST CBPs) in Salmonella spp. from pig carcass swab samples (n=9) in 2015 ...... 35

Figure 4.1: Resistance and susceptibility (interpreted using BSAC CBPs) of E. coli isolates from mastitis infections of cattle, 2013-2015 ...... 37

Figure 4.2: Resistance and susceptibility (interpreted using BSAC CBPs) of S. dysgalactiae isolates from mastitis infections of cattle, 2013-2015 ...... 38

Figure 4.3: Resistance and susceptibility (interpreted using BSAC CBPs) of S. uberis isolates from mastitis infections of cattle, 2013-2015 ...... 38

Figure 4.4: Resistance and susceptibility (interpreted using BSAC CBPs) of S. aureus isolates from mastitis infections of cattle, 2013-2015 ...... 39

Figure 4.5: Resistance and susceptibility (interpreted using BSAC CBPs) of P. multocida isolates from respiratory infections of cattle, 2013-2015 ...... 40

Figure 4.6: Resistance and susceptibility (interpreted using BSAC CBPs) of M. haemolytica isolates from respiratory infections of sheep, 2013-2015 ...... 41

Figure 4.7: Resistance and susceptibility of Brachyspira hyodysenteriae isolates from pigs in England and Wales to tiamulin, 2010-2015 ...... 43

Figure 4.8: Resistance and susceptibility (interpreted using BSAC human clinical breakpoints) of S. suis isolates from pigs, 2013-2015 ...... 44

Figure 4.9: Resistance (interpreted using BSAC CBPs) in E. coli from cattle (all ages) in 2013, 2014 and 2015 ...... 49

List of Figures

Figure 4.10: Resistance (interpreted using BSAC CBPs) in E. coli in 2015 from cattle (by age category ...... 50

Figure 4.11: Resistance (interpreted using BSAC CBPs) in E. coli from pigs (all ages) in 2013, 2014 and 2015 ...... 51

Figure 4.12: Resistance (interpreted using BSAC CBPs) in E. coli from pigs in 2015 (by age category) in 2015 ...... 52

Figure 4.13: Resistance (interpreted using BSAC CBPs) in E. coli from sheep (all ages) in 2013, 2014 and 2015 ...... 53

Figure 4.14: Resistance (interpreted using BSAC CBPs) in E. coli from sheep in 2015 (by age category) ...... 54

Figure 4.15: Resistance (interpreted using BSAC CBPs) in E. coli from chickens in 2013, 2014 and 2015 ...... 55

Figure 4.16: Percentage of Salmonella isolates from key animal species which were resistant to one or more antibiotics, 2013-2015 ...... 57

Figure 4.17: The top ten most commonly isolated Salmonella serovars from livestock in 2013-2015 ...... 59

Figure 4.18: Salmonella Typhimurium: percentage of resistant isolates in 2013 (n=165), 2014 (n=224) and 2015 (n=165) ...... 61

Figure 4.20: Salmonella other than Dublin and Typhimurium, percentage of isolates resistant to antibiotics tested in 2013 (n=2328), 2014 (n=1837) and 2015 (n=2198) ...... 63

Figure A1.2: Milligrams (mg) of active ingredient of antibiotic sold for food producing species per Population Correction Unit (PCU) 2011-2015 calculated using the ESVAC and original UK-VARSS methodology ...... 69

Figure A1.3: Milligrams (mg) of active ingredient of antibiotic sold for food producing species per Population Correction Unit (PCU) 2005-2015 using the ESVAC methodology ...... 70

Figure A4.1: Tonnes of active ingredient of antibiotic used by all members of the BPC Antibiotic Stewardship Scheme 2012-2015 ...... 76

Figure A4.2: Tonnes of active ingredient of antibiotic sold indicated for use in all farmed food producing species only, indicated for use in poultry only + both pigs and poultry only and used by members of the BPC Antibiotic Stewardship Scheme 2012-2015 ...... 77

Figure A4.3: Percentage of active ingredient of antibiotic used by members of the BPC Antibiotic Stewardship Scheme by class 2015 ...... 78

Figure A4.4: Tonnes of active ingredient of fluoroquinolones used by members of the BPC Antibiotic Stewardship Scheme 2014-2015 ...... 79

List of Tables

Table 1.1: Kilograms (kg) and (average amount in grams per dairy cow*) of active ingredient of intramammary antibiotics sold 2011-2015 ...... 21

Table 1.2: Tonnes of active ingredient of antibiotic sold for all species by class and total sales 2011- 2015 ...... 22

Table 1.3: Tonnes and (% of total sales) of active ingredient of antibiotic sold by species category indicated and total sales 2011-2015 ...... 25

Table 1.4: Tonnes of active ingredient of antibiotic sold for farmed food producing species only, by species category indicated 2011-2015 ...... 26

Table 1.5: Tonnes and (% of total sales) of active ingredient of antibiotic sold for all species by route of administration 2011-2015 ...... 26

Table 3.1: Resistance in E. coli (interpreted using both CBPs and ECVs) from pig caecal samples in 2015 ...... 34

Table 3.2: Results of specific testing for ESBL producing E. coli in pig caecal samples following selective culture in 2015 ...... 34

Table 4.1: Findings of LA-MRSA in the UK by government laboratories, 2013-2015 ...... 45

Table 4.2: Resistance in all Escherichia coli isolates from cattle, pigs, sheep, broilers and turkeys (all ages, combined) from 2013-2015 ...... 46

Table 4.3: Resistance in Salmonella Dublin: percentage of resistant isolates in 2013, 2014 and 2015 ...... 60

Table A1.1: Differences between the ESVAC and VARSS methodology used in previous publications for the calculation of quantity of antibiotic sold ...... 67

Table A1.2: Comparison of UK-VARSS and ESVAC methodology for the calculation on tonnes of active ingredient sold, Population Correction Unit (PCU), and milligrams (mg) of active ingredient sold per PCU for food producing species, 2011-2015...... 69

Table A1.3: Tonnes of active ingredient of antibiotic sold for all species by “other” routes of administration 2011-2015 ...... 70

Table A2.1: Number of livestock (in thousands) by food producing species 2011-2015 ...... 71

Table A2.2: Population correction unit (PCU) (in thousand tonnes) by food producing species and total 2011-2015 ...... 72

Table A2.3: Average weights at time of treatment (kg) used to calculate the Population Correction Unit (PCU) ...... 73

List of Tables

Table A4.1: Tonnes of active ingredient of antibiotic sold indicated for use in all farmed food producing species only, indicated for use in poultry only + both pigs and poultry only and used by members of the BPC Antibiotic Stewardship Scheme 2012-2015* ...... 78

Table A4.2: Tonnes of active ingredient of antibiotic used by members of the BPC Antibiotic Stewardship Scheme by class 2015 ...... 79

Table A8.1: Antibiotic disc concentrations used in Northern Ireland ...... 86

Table A9.1: Recovery of ESBL producing E. coli from pig caeca in 2015, compared with results from a 2013 pig survey ...... 87

Table A10.1: Resistance in nine Salmonella spp. from pig caecal samples in 2015 ...... 88

Table A11.1: Resistance (interpreted using BSAC CBPs) in Escherichia coli mastitis isolates, 2013- 2015 ...... 89

Table A11.2: Resistance (interpreted using BSAC CBPs) of staphylococci and streptococci from mastitis cases, 2013-2015 ...... 90

Table A12.1: Resistance (interpreted using BSAC CBPs) of Pasteurella multocida and Mannheimia haemolytica from respiratory infections of cattle, 2013-2015 ...... 91

Table A12.2: Resistance (interpreted using BSAC CBPs) of Histophilus somni and Trueperella pyogenes from respiratory infections of cattle, 2013-2015 ...... 92

Table A13.1: Resistance (interpreted using BSAC CBPs) of Pasteurella multocida and Actinobacillus pleuropneumoniae from respiratory infections of pigs, 2013-2015 ...... 93

Table A14.1: Resistance (interpreted using BSAC CBPs) of Pasteurella multocida and Mannheimia haemolytica from sheep, 2013-2015...... 94

Table A14.2: Resistance (interpreted using BSAC CBPs) of Bibersternia trehalosi and Trueperella pyogenes from sheep, 2013-2015 ...... 95

Table A15.1: MIC values of Brachyspira hyodysenteriae isolates from infections of pigs to tiamulin, 2010-2015 ...... 96

Table A15.2: Resistance (interpreted using BSAC CBPs) of Streptococcus suis from infections of pigs, 2013-2015 ...... 97

Table A15.3: Resistance (interpreted using BSAC CBPs) of Staphylococcus aureus from infections of chickens, 2013-2015 ...... 97

Table A15.4: Resistance (interpreted using BSAC CBPs) of Erysipelothrix rhusiopathiae from infections of pigs, 2013-2015 ...... 98

Table A15.5: Resistance (interpreted using BSAC CBPs) of Listeria monocytogenes from infections of sheep, 2013-2015 ...... 98

List of Tables

Table A15.6: Resistance (interpreted using BSAC CBPs) of Streptococcus dysgalactiae from infections of sheep, 2013-2015 ...... 99

Table A16.1 – Resistance in all E. coli from cattle, sheep, pigs, chickens and turkeys (combined) in England & Wales, Northern Ireland and Scotland ...... 100

Table A16.2 – Resistance in all E. coli from cattle (all ages) in England & Wales, Northern Ireland and Scotland ...... 101

Table A16.3 – Resistance in all E. coli from pigs (all ages) in England & Wales, Northern Ireland and Scotland ...... 102

Table A16.4 – Resistance in all E. coli from sheep (all ages) in England & Wales, Northern Ireland and Scotland ...... 103

Table A16.5 – Resistance in all E. coli from chickens (all ages) in England & Wales, Northern Ireland and Scotland ...... 104

Table A16.6 – Resistance in all E. coli from turkeys (all ages) in England & Wales, Northern Ireland and Scotland ...... 105

Table A16.7 – Resistance in E. coli from cattle in England & Wales, Northern Ireland and Scotland in 2013 ...... 106

Table A16.8 – Resistance in E. coli from cattle in England & Wales, Northern Ireland and Scotland in 2014 ...... 107

Table A16.9 – Resistance in E. coli from cattle in England & Wales, Northern Ireland and Scotland in 2015 ...... 108

Table A16.10 – Resistance in E. coli from pigs in England & Wales, Northern Ireland and Scotland in 2013 ...... 109

Table A16.11 – Resistance in E. coli from pigs in England & Wales, Northern Ireland and Scotland in 2014 ...... 110

Table A16.12 – Resistance in E. coli from pigs in England & Wales, Northern Ireland and Scotland in 2015 ...... 111

Table A16.13 – Resistance in E. coli from sheep in England & Wales, Northern Ireland and Scotland in 2013 ...... 112

Table A16.14 – Resistance in E. coli from sheep in England & Wales, Northern Ireland and Scotland in 2014 ...... 113

Table A16.15 – Resistance in E. coli from sheep in England & Wales, Northern Ireland and Scotland in 2015 ...... 114

Table A17.1: Resistance in all Salmonella from cattle, pigs, sheep, chickens and turkeys (combined) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 .. 115

List of Tables

Table A17.2: Resistance in all Salmonella from cattle (all ages) from surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 ...... 116

Table A17.4: Resistance in all Salmonella from sheep (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 ...... 118

Table A17.5: Resistance in all Salmonella from chickens (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 ...... 119

Table A17.6: Resistance in all Salmonella from turkeys (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 ...... 120

Table A17.7: Resistance in all Salmonella Dublin from cattle, pigs, sheep, chickens and turkeys (combined) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013- 2015 ...... 121

Table A17.8: Resistance in all Salmonella Typhimurium from cattle, pigs, sheep, chickens and turkeys (combined) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 ...... 122

Table A17.9: Resistance in all Salmonella other than Dublin and Typhimurium from cattle, pigs, sheep, chickens and turkeys (combined) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015 ...... 123

Table A17.10: Top ten Salmonella serovars isolated in Northern Ireland between 2013-2015 124

Table A17.11: Top ten Salmonella serovars isolated in Scotland between 2013-2015 ...... 124

Executive Summary

Executive Summary Antibiotic sales All figures calculated using the European agreed ESVAC method unless specified.

Overall trends in mg/kg (using population correction unit)

This year the methodology used to calculate national sales data trends for this report has been changed so it is harmonised and consistent with methodology used across European countries. Between 2014 and 2015, antibiotics for use in food producing animals (in mg/PCU) decreased by 10% from 62 to 56 mg/PCU. Sales of highest priority critically important antibiotics remain low and were little changed compared to 2014: sales of 3rd and 4th generation cephalosporins were 0.17mg/PCU in 2015 (compared to 0.19mg/PCU in 2014) and sales of fluoroquinolones were 0.34mg/PCU in 2015 (compared to 0.35 mg/PCU in 2014). Colistin was included as a critically important antibiotic for the first time in this year’s UK-VARSS report, following the discovery of the plasmid mediated resistance gene mcr-1 in China in November 2015. Sales of colistin in the UK were 0.12mg/PCU, which is below the European Medicines Agency’s Antimicrobial Expert Group’s recommended target of 1mg/PCU.

Total sales in tonnes of active ingredient by class

*excludes 3rd & 4th generation cephalosporins (shown separately) **other includes: amphenicols, lincomycins, pleuromutilins, steroidal antibiotics and polymixins (excl. colistin - shown separately)

Executive Summary

Total sales in tonnes of active ingredient by species indicated

The mg/PCU for products only authorised for use in pigs and/or poultry decreased by 16% between 2014 and 2015, from 192 mg/PCU to 162 mg/PCU.

Antibiotic Usage and Data Collection Activities by Livestock Species

In order to optimise usage of antibiotics in livestock it is important to monitor antibiotic use in each species. The VMD has been working with the poultry, pig and cattle sectors to develop systems to monitor their antibiotic usage. Highlights include:

The British Poultry Council reported that use of antibiotics by members of its Antibiotic Stewardship Scheme in 2015 reduced by 27% compared to 2014, including a 52% reduction in the use of fluoroquinolones.

Agriculture and Horticulture Development Board pork reported that, by the end of October 2016, 534 sites had signed up to their online reporting system eMB-Pigs, covering 17% of national pig production (2,544,186 finishers, 2,988,379 weaners and 371,580 sows and boars).

The Cattle Health and Welfare Group completed a scoping study to investigate current data recording systems and have developed a proposal for a data capture system, that should be operational by 2017.

Executive Summary

Antibiotic Resistance

Percentage resistance in E. coli from randomly selected healthy pigs

In 2015, isolates of E. coli from the caeca of healthy pigs randomly selected at slaughter were tested for resistance. Of the 150 isolates of E. coli tested, 1% were resistant to ciprofloxacin; none were resistant to cefotaxime, ceftazidime or colistin. However, following enrichment, presumptive extended spectrum ß-lactamase (ESBL) producing E. coli were detected in 24.7% of 327 caecal samples. No carbapenemase or OXA-48 producing E. coli were detected in 294 caecal samples cultured on selective agar.

* To note this testing does not identify the type or number of ESBLs present

Salmonella isolates resistant to one or more antibiotic (%) from clinical surveillance

In total, 1594 Salmonella isolates from cattle, sheep, pigs, chickens and turkeys were tested. Resistance to the highest priority critically important antibiotics was very low with 1.3% (20/1594) of all Salmonella from all species resistant to ciprofloxacin (FQ) and 0.1% were resistant to cefotaxime and ceftazidime.

n= number of samples tested FQ = fluoroquinolones

Executive Summary

Resistance level in mastitis pathogens (%) from clinical surveillance

Resistance demonstrated by bovine mastitis pathogens was broadly similar to previous years. Resistance to antibiotics commonly used in the treatment of mastitis did occur but varied between pathogens, highlighting the value of culture and sensitivity testing in the treatment of mastitis cases.

n = number of samples tested

Other observations of interest

 0.6% of 313 samples from randomly sampled pigs, and 1.2% of 163 isolates from clinical surveillance, were positive for the mcr-1 gene.

 Overall the level of resistance was low in bacteria associated with respiratory disease in sheep and cattle.

 Resistance to tiamulin in Brachyspira hyodysenteriae has been highlighted in previous reports due to the serious impact it could have on pig health and welfare. Of the five isolates tested in 2015, one was resistant.

 Livestock-associated meticillin-resistant S. aureus (LA-MRSA) ST398 was detected in a pooled caecal sample from pigs, collected at slaughter as part of a research project.

 None of the 63 isolates of Streptococcus suis that were tested were resistant to penicillin.

 E. coli isolates from a combination of all livestock species were most frequently resistant to streptomycin, tetracycline and ampicillin. Resistance to the highest priority critically important antibiotics tested was generally low, with 9.3% resistant to cefotaxime, 7.2% resistant to cefpodoxime, and 10.7% resistant to enrofloxacin.

Introduction

Antimicrobial resistance has continued to maintain its high profile internationally at the highest levels in 2016, culminating in the adoption of a declaration on AMR at the 71st General Assembly of the United Nations in New York in September. 2016 also saw the World Organisation for Animal Health (OIE) draw together its many workstreams on AMR into an adopted strategy for Combatting Antimicrobial Resistance through a One Health Approach (OIE, 2016) and the United Nations Food and Agriculture Committee adopt its Action Plan on Antimicrobial Resistance 2016-2020 (FAO, 2016). In Europe, 2016 represents the final year of the European Commission’s five year Action Plan against the Rising Threats from Antimicrobial Resistance, and the Commission recently announced its intention to propose a new action plan in 2017 with the objective of preserving the efficacy of antimicrobials for humans and animals, and identifying coherent action to that end (European Commission, 2016).

The past year saw publication of the final report and recommendations of the AMR Review chaired by Lord Jim O’Neill (Review on AMR, 2016), an independent review with a focus on economic aspects of AMR, which was commissioned in 2014 by the previous Prime Minister. The government published its formal response to the review, setting out how the recommendations would be taken forward. For animal health, the three highest profile government commitments are around the introduction of targets for the reduction of antibiotic use in animals, and strengthening stewardship in animals of antibiotics which are of greatest importance to human health. As set out in the UK’s 5 Year AMR Strategy, high levels of animal health and welfare and good disease control are essential factors in underpinning the success of these ambitions in a long-term and sustainable way.

The first two chapters report on the data available and the data which will become available, for measuring the success of reducing antibiotic use. Our top-level multi-species target is to reduce antibiotic use from 62 mg/kg (2014 data) to 50 mg/kg by 2018. We report a reduction of approximately 10%. This is a good step towards the 50 mg/kg target; while antibiotic use can fluctuate with a number of external factors such as disease outbreaks in a given year, differing degrees of reduction have been seen across the board in products authorised for different species and for all major classes of antibiotics.

The question remains, how appropriately low is possible for antibiotic use? This is where engagement with the veterinary profession and farming industry is critical. We are committed to have industry-led, sector-specific targets for reduction in antibiotic use in place by 2017. The introduction to last year’s VARSS report highlighted the potential opportunity for data on consumption of antibiotics by different animal species to be collected, together with information on health/disease status of the animals. Such systems are now being put in place. Recognising that for data to be useful to vets and farmers at a local and farm level, sectors may identify measures/ parameters which will be of most use for informing and encouraging reduction of antibiotic use in the context of responsible use and optimal stewardship of antibiotics. It’s also clear that different sectors are at different stages in developing such monitoring systems. While the focus will remain on the three priority sectors of pigs, poultry and cattle, optimal stewardship of antibiotics is a

Introduction

responsibility in every species and we look forward to seeing how the other animal sectors rise to this challenge.

The EU harmonised monitoring programme, which evaluates resistance in bacteria of public health importance which have been isolated from healthy animals, recognises the potential for certain bacteria to present a route of AMR transmission from animals to people. This programme is designed to give results representative of each country’s pig population and uses methodology harmonised across Europe. The findings for 2015 will be published by EFSA next February in the annual “Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food”.

In line with previous years’ format, the final chapter reports antibiotic resistance results from clinical samples taken from veterinary patients in England and Wales. However, for the first time this year we have included resistance data for E. coli and Salmonella from Scotland and Northern Ireland, courtesy of colleagues in those Devolved Administrations. Work remains to harmonise methodology for determining resistance.

2016 has been a year of building momentum, reaffirming and updating old commitments, and making new ones. There has been much action by the veterinary profession and in the key livestock species sectors which has contributed to the 10% reduction of antibiotic sales during 2015. However, currently the only sector that can evidence this is the meat poultry industry. That is because they have the antibiotic use data to show accurately what antibiotics were used in meat poultry, and by doing this in tandem with implementation of their stewardship plan, have been able to explain how these reductions have been achieved. Other sectors are on their way to achieving this.

We very much look forward to continuing to work collaboratively with all interested parties to maintain momentum generated, and we also very much look forward to next year’s VARSS report in anticipation of further insights into our collective progress on improving the responsible use of antibiotics in animals.

Professor S. Peter Borriello Chief Executive Officer

Chapter 1: Sales of Veterinary Antibiotics

Introduction

The quantity of authorised veterinary antibiotics sold throughout the UK has been reported to the VMD by pharmaceutical companies since 1993 and this has been a statutory requirement since 2005 (Annex 1). The data represented do not take into account wastage, imports or exports of veterinary antibiotics, but they serve as the best currently available approximation of the quantity of antibiotics administered to animals in the UK. The VMD sends these data annually to the European Medicines Agency, where they are collated with equivalent data from other European countries and published in the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) report on sales of veterinary antibiotics in 29 European countries. In keeping with most other European countries, the UK does not yet have a comprehensive system which can collect and collate data on antibiotic use by animal species. However, such systems are under development and discussed further in Chapter 2.

Method

In previous UK-VARSS reports (2013 and 2014) the methodology used for the calculation of the amount of active ingredient in each antibiotic product, and the mg/PCU calculation, has differed from the European methodology, as used in the annual ESVAC reports. In order to provide harmonisation, the quantity of active ingredient sold will now be reported using the European methodology, which has been developed and implemented by ESVAC. All sales data published in this chapter have been updated to reflect these changes. An explanation of the changes to the methodology can be found in Annex 1.

Annual sales of all authorised veterinary medicines are supplied by Marketing Authorisation Holders (MAH) to the VMD, where they are collated and validated. From these data, the total weight in tonnes of each antibiotic active substance is calculated. The data reported here are presented according to the ATCvet classification system (www.whocc.no/atcvet/). Antibiotic agents for intestinal use, intrauterine use, systemic use and intramammary use are included, but sales of dermatological preparations and preparations for sensory organs (described as “other” route of administration in previous UK-VARSS reports) are not included.

Trends in sales of antibiotics between years and between different countries cannot be determined without taking into consideration variations in the number and size of the animals that may have been treated. Therefore sales data are analysed using the Population Correction Unit (PCU), a theoretical technical unit of measurement adopted by countries across Europe to standardise sales against the animal population denominator. Using the PCU, the overall sales of products authorised for use in food producing species can be presented as mg/PCU. This enables year-on–year, and country, comparisons to be made. Further details on these calculations are presented in Annex 2 and full technical details on PCU methodology can be found in the 2009 ESVAC report (ESVAC, 2011).

Chapter 1: Sales of Veterinary Antibiotics

There are a number of limitations when analysing sales data. They cannot, for example, tell us the number, dose and duration of treatments or the extent to which prescribing was appropriate or inappropriate. Reducing treatment duration or dose, for example, would be likely to represent inappropriate prescribing. Further, the results do not tell us whether antibiotics were prescribed for treatment, metaphylaxis or preventative use.

From sales data it is also not possible to identify the species in which the antibiotics were used. This is for two reasons:

1. Many products are authorised for use in more than one animal species. In particular, a large number of products are authorised for use in both pigs and poultry. 2. The ‘prescribing cascade’ makes provision that, under certain circumstances, medicines may legally be administered to species for which they have not been authorised. This is known as ‘off-label’ use, and there is no way of knowing what proportions of products sold have been administered under the cascade in this way. More details on the cascade are available in Annex 5.

Contributing pharmaceutical companies are listed in Annex 21.

Sales of Antibiotics for Food Producing Animals

The mg/PCU figure is the most appropriate parameter to use when comparing antibiotic sales year- on-year, as it considers changes in the number and relative size of animals in the population. The mg/PCU can be considered as the average quantity of active substance sold per kilogram bodyweight of food producing animal treated in the UK over the course of the year.

The mg/PCU figure for all food producing species decreased by 10% (6mg/PCU) between 2014 and 2015, and the combined pig and poultry mg/PCU decreased by 16% (30mg/PCU). These are the second lowest figures reported over the last five years. However the lowest figures (in 2011) are considered to be artificially low due to changes in Marketing Authorisation Holder for a small number of food-producing animal products between 2010 and 2011, which led to stockpiling in 2010 (due to concerns about availability) and subsequently lower purchasing during 2011. This is discussed in more detail in the 2012 VARSS report (VMD, 2013).

Chapter 1: Sales of Veterinary Antibiotics

Figure 1.1: Milligrams (mg) of active ingredient of antibiotic sold for pigs and/or poultry only and all food producing species per Population Correction Unit (PCU) 2011-2015 (calculated using ESVAC methodology, see Annex 1 for more detail)

Pigs and/or Poultry Only All Food Producing Species

250

197 200 192 182 162 149 150

100

66 62 62 51 56

Active ingredient (mg/PCU) ingredient Active 50

0 2011 2012 2013 2014 2015

Antibiotics of Particular Relevance to Human Health

Certain antibiotic classes are categorised by the World Health Organisation (WHO) as critically important antibiotics (CIA) for human use, of which macrolides, fluoroquinolones and 3rd and 4th generation cephalosporins are designated as ‘highest priority critically important antibiotics’ (HP- CIA) (WHO, 2011). In December 2014, the European Medicines Agency (EMA) published scientific advice on the risk to humans from antibiotic resistance caused by the use of HP-CIAs in animals. This advice classed macrolides as category 1, which means the risk of use in animals to public health is low or limited, whereas fluoroquinolones and 3rd and 4th generation cephalosporins were classified as category 2, which means the risk for public health is considered higher. This advice was subsequently updated to take into account new data on colistin resistance, and the expert group recommended that colistin was moved to category 2, alongside fluoroquinolones and 3rd and 4th generation cephalosporins.

On this basis, the presentation of more detailed information on antibiotics of relevance to human health is focused on fluoroquinolones, 3rd and 4th generation cephalosporins and colistin. Figure 1.2 shows the sales of these antibiotics in mg/PCU. Sales of HP-CIAs make up a small proportion of the 56 mg/PCU overall all-antibiotic use in livestock and have remained stable over the last 5 years.

Chapter 1: Sales of Veterinary Antibiotics

Figure 1.2: Milligrams (mg) of active ingredient of “highest priority critically important antibiotics’’ sold for food producing species per Population Correction Unit (PCU) 2011-2015

Sales of Veterinary Antibiotics Containing Colistin

Following the discovery, in China in November 2015, of a novel colistin resistance gene capable of horizontal transmission (mcr-1) the European Medicines Agency (EMA) Antimicrobial Expert Group (AMEG) updated their advice to the European Commission (EC) on the use of colistin products in animals and the development of resistance, and any possible impact on human and animal health. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_00 0639.jsp&

The expert group recommended that colistin should be added to the AMEG list of higher risk critically important antibiotics (category 2) that currently includes fluoroquinolones and 3rd and 4th generation cephalosporins. The AMEG’s advice also recommended that, for countries which are “high and moderate” consumers of colistin, a target for reduction should be set at 5 mg/PCU, whereas for countries whose use is already below this level, the target should be set at 1 mg/PCU. The AMEG were clear that these targets should be met without increasing the use of fluoroquinolones, 3rd and 4th generation cephalosporins or overall consumption of antimicrobials.

The sales of veterinary antibiotic products containing colistin in the UK are low and have remained stable over the past five years, with less than 1 tonne being sold annually, and the mg/PCU staying consistently well below the lower recommended 1mg/PCU target.

The finding of the mcr-1 gene in China, and subsequently in the UK and other countries across the world (Vet Times, 2015) was published at the end of 2015. For this reason, the 2015 UK sales data reported here will not reflect voluntary measures that the UK livestock industries took to reduce colistin use after the discovery of the novel resistance was reported. 20

Chapter 1: Sales of Veterinary Antibiotics

Sales of Intramammary Antibiotic Products

Table 1.1 and Figure 1.3 below show that the sales of products for lactating cows decreased by 6% (80kg of active substance) and the average amount per dairy cow decreased by 9% (0.06g/animal) between 2014 and 2015. This is the lowest level reported over the last 5 years. Sales of dry cow products have remained stable between 2014 and 2015.

Table 1.1: Kilograms (kg) and (average amount in grams per dairy cow*) of active ingredient of intramammary antibiotics sold 2011-2015

2011 2012 2013 2014 2015 Dry Cow 1698 (0.95) 1895 (1.06) 1716 (0.96) 1782 (0.97) 1898 (1.0) Products Lactating 1417 (0.79) 1750 (0.97) 1331 (0.75) 1289 (0.70) 1209 (0.64) Cow Products Total 3114 (1.73) 3645 (2.03) 3047 (1.71) 3072 (1.67) 3107 (1.64)

*based on number of dairy cows in the national herd in each respective year

Figure 1.3: Average annual amount in grams (g) of active ingredient of intramammary antibiotic sold per dairy cow 2011-2015

Dry cow products Lactating cow products Total 2.5

1.5

0.5 Active ingredient per dairy cow per year (g) year per cowdairy per ingredient Active

0 2011 2012 2013 2014 2015

Chapter 1: Sales of Veterinary Antibiotics

Total Sales by Weight and Antibiotic Group (indicated for all species)

The total quantities of antibiotic active substance in products sold between 2011 and 2015, and their breakdown by class, are shown in Table 1.2 and Figure 1.4. Definitions of these classes, and the active ingredients that are included, can be found in Annex 3. The total quantity of antibiotics sold in 2015 was 404 tonnes, which is a decrease of 9% from 2014. As previously discussed, however, tonnage is a less meaningful way of monitoring trends than mg/PCU as it does not take into account variations in UK livestock weights and numbers.

Table 1.2: Tonnes of active ingredient of antibiotic sold for all species by class and total sales 2011-2015

2011 2012 2013 2014 2015 Tetracyclines 115 201 194 181 166 Trimethoprims/ Sulphonamides 72 80 61 71 68 Trimethoprims 12 13 10 12 11 Sulphonamides 60 66 51 59 57 ß-lactams 89 94 94 95 80 1st/2nd Generation Cephalosporins 5 5 5 5 5 (t) 1 1 1 1 1 3rd/4th Generation Cephalosporins (kg)* 1166 1328 1192 1332 1202 Penicillins** 20 19 20 12 9 Other Penicillins*** 63 69 68 77 65 Aminoglycosides 20 22 24 24 23 Streptomycins 9 10 11 9 10 neomycin and framycetin 1 1 1 1 1 Other aminoglycosides**** 9 12 9 14 13 Macrolides 37 41 40 48 36 (t) 2 2 3 3 3 Fluoroquinolones (kg)* 2084 2381 2562 2590 2529 Other***** 22 24 21 24 27 (t) 0.87 0.61 0.73 0.84 0.87 Colistin (kg)* 866 606 728 837 870 Total 357 464 436 445 404×

*Because of the heighted interest in HP-CIA classes the sales of fluoroquinolones, 3rd and 4th generation cephalosporins and colistin are displayed in kg as well as tonnes. **includes benzylpenicillin, benzathine penicillin, phenoxymethylpenicillin, procaine penicillin ***includes amoxicillin (including in combination with clavulanic acid), ampicillin, cloxacillin, nafcillin ****includes apramycin, gentamycin, kanamycin, spectinomycin *****includes: amphenicols, lincomycins, pleuromutilins, polymixins and steroidal antibiotics. Colistin sales are included within this group. × For each of the antibiotic classes, the total was rounded to the nearest integer. This explains the discrepancy between the overall total and the classes’ totals.

Chapter 1: Sales of Veterinary Antibiotics

The sales of different classes of antibiotics in 2015 are shown in Figure 1.4, which highlights that tetracyclines, β-lactams (including penicillin) and trimethoprim/sulphonamides account for the majority (>75%) of active substances sold.

Figure 1.4: Percentage of active ingredient of antibiotic by class sold for all species in 2015

Trimethoprims/ Macrolides Sulphonamides 9% 17% Other** 6% Highest Priority Critically Important Aminoglycosides Antibiotics Other ß-lactams 6% Fluoroquinolones 1% 20% 3rd/4th gen cephs <1% Colistin <1%

Tetracyclines 41%

**Other includes: amphenicols, lincomycins, pleuromutilins, polymixins and steroidal antibiotics.

In 2015, there was a decrease in the sales of all antibiotic classes, with the exception of the group of products classified as ‘other’ (Fig. 1.5). Note that, as described in the 2012 VARSS report, the tetracycline sales in 2011 are considered to be artificially low due to stockpiling in 2010 (caused by concerns about availability following a change in Marketing Authorisation Holder) and subsequently lower purchasing during 2011. This is discussed in more detail in the 2012 VARSS report.

Chapter 1: Sales of Veterinary Antibiotics

Figure 1.5: Milligrams (mg) of active ingredient of antibiotic by class sold for food producing species per Population Correction Unit (PCU) by class in 2011-2015

Tetracyclines Trimethoprims/Sulphonamides Other** Fluoroquinolones Colistin Other beta-lactams Macrolides Aminoglycosides 3rd/4th generation cephalosporins 35

15 Active Ingredient (mg)/PCU Ingredient Active

0 2011 2012 2013 2014 2015

**Other includes: amphenicols, lincomycins, pleuromutilins, polymixins and steroidal antibiotics.

Chapter 1: Sales of Veterinary Antibiotics

Sales by Animal Species Indicated

The quantities of antibiotic active substance in products sold between 2011 and 2015 are shown in Table 1.3 and Table 1.4, differentiated by the species or combination of species for which they are indicated. In the UK, the role of horses is predominantly as a companion or sport animal and therefore horses pose limited public health risk from food borne transmission. For this reason, in tables 1.3 and 1.4 horses are grouped with companion animals while farmed food producing species are grouped together. Please note, however, that when calculating the mg/PCU, horses are included as a food producing species, in line with ESVAC methodology (see Annex 1).

Table 1.3: Tonnes and (% of total sales) of active ingredient of antibiotic sold by species category indicated and total sales 2011-2015

2011 2012 2013 2014 2015

Indicated for farmed food 300 (84%) 396 (85%) 368 (84%) 383 (86%) 344 (85%) producing animals only

Indicated for companion 34 (10%) 35 (8%) 36 (8%) 32 (7%) 25 (6%) animals and/or horses only

Indicated for a combination of both food and non-food 23 (6%) 33 (7%) 32 (7%) 30 (7%) 35 (9%) producing species

Total sales of antibiotics 357 464 436 445 404

The proportions of antibiotics sold across each of the three categories above have remained similar over the past five years.

In 2015, 87% of active substance sales from antibiotic products authorised only for farmed food producing animals were for pigs and/or poultry, and no other species (Table 1.4). Products for multiple livestock species (excluding those authorised solely for pigs and/or poultry) accounted for 8% of antibiotics sold for farmed food producing animals in 2015 (Table 1.4).

Chapter 1: Sales of Veterinary Antibiotics

Table 1.4: Tonnes of active ingredient of antibiotic sold for farmed food producing species only, by species category indicated 2011-2015

Product indicated 2011 2012 2013 2014 2015 exclusively for: Pigs and poultry only 154 235 217 235 212 Pigs only 64 66 63 66 50 Poultry only* 41 47 43 43 38 Multiple farmed food 27 32 30 24 28 producing species** Cattle only 12 14 14 13 14 Fish only 2.1 2.1 0.8 2.4 0.7 Sheep only 0.1 0.2 0.2 0.1 0.2

*In previous reports, products authorised for use in ‘ducks’ in combination with other poultry species have been included in the ‘multiple livestock species’ category. These products have been included in the ‘poultry only’ category in this table and all historical data have been updated. This change affects those data reported in previous UK-VARSS reports for ‘pig and poultry only’, ‘poultry only’ and ‘multiple farmed food producing species’

** Not including products indicated for pigs and poultry only, horses or products indicated for a combination of both farmed food and non-food producing species.

Sales by Route of Administration

The main routes of administration of veterinary antibiotics sold for all species in 2011-2015 are listed in Table 1.5 and shown in Figure 1.6. Premixes and oral/water soluble products (not including tablets) accounted for 57% and 26% respectively of the total antibiotics sold in 2015.

Table 1.5: Tonnes and (% of total sales) of active ingredient of antibiotic sold for all species by route of administration 2011-2015

2011 2012 2013 2014 2015 Premix 195 (55%) 287 (62%) 263 (60%) 281 (63%) 232 (57%) Oral/Water* 103 (29%) 108 (23%) 109 (25%) 100 (22%) 105 (26%) Injectable 43 (12%) 49 (11%) 47 (11%) 45 (10%) 51 (13%) Tablets 13 (4%) 16 (3%) 14 (3%) 16 (4%) 12 (3%) Intramammary 3 (<1%) 4 (<1%) 3 (<1%) 3 (<1%) 3 (<1%) Total 357 464 436 445 404

* Excluding tablets

Chapter 1: Sales of Veterinary Antibiotics

Figure 1.6: Percentage of active ingredient of antibiotic sold for all species by route of administration 2011-2015

40 Premix Oral/Water Injectable 30 Tablet

10 Percentage Active Ingredient of Total Sales (%) Total Sales of Ingredient Active Percentage

0 2011 2012 2013 2014 2015

Chapter 2: Data Collection Activities to determine the level of Antibiotic Usage by Livestock Species

Introduction

Antibiotic usage refers to the amount of antibiotics purchased, prescribed and/or administered. Many antibiotics are authorised for use in multiple species, so it is not possible to determine how much is used per species from sales data. The VMD is therefore working in partnership with key livestock sectors to develop, facilitate and coordinate collection systems for the priority livestock species (pigs, poultry and cattle).

Capturing antibiotic usage data per species will provide a baseline against which trends and the effect of interventions, such as those designed to reduce antibiotic use, can be measured. The data can also be used to investigate risk factors for high levels of antibiotic use and the effect of use on the development of resistance. Collection systems will also allow for benchmarking, enabling farmers to compare themselves with their peers and encouraging vets and farmers to identify and share good practice.

This chapter describes the progress achieved so far, with updates from each of the priority livestock sectors. For the second year running, total antibiotic usage has been provided by the British Poultry Council (BPC) and this is presented in Annex 4.

Poultry

Contribution from the British Poultry Council:

The British Poultry Council (BPC) represents more than 90% of the UK poultry meat production, and its Antibiotic Stewardship Scheme was established in 2011. This involved the formation of an expert working group of poultry meat producers and poultry veterinarians to identify a programme of work designed to promote the responsible use of antibiotics. One of the first actions of this group in 2012 was to ban the use of all cephalosporins in flocks used for poultry meat production, and to establish its commitment to stop the prophylactic use of fluoroquinolones in day old chickens. In 2015, the BPC membership stopped the use of colistin in its flocks, and in 2016, a further commitment was made to stop the prophylactic use of fluoroquinolones in day old chickens. In 2014, BPC members became the first livestock sector to voluntarily submit to the VMD antibiotic usage data collected from poultry meat producers. These data (Annex 4) show that members of the BPC Antibiotic Stewardship Scheme reduced their use in 2015 by 27% compared to 2014, which included a 52% reduction in the use of fluoroquinolones. Furthermore over the period 2012-2015, BPC members decreased total antibiotic use by 43%.

Chapter 2: Data Collection Activities to determine the level of Antibiotic Usage by Livestock Species

Contribution from the British Egg Industry Council:

The egg sector has commenced the second year of data collection, where all egg producers, pullet rearers and breeding companies are required to report any use of an antibiotic to their subscriber. This data is reported to the BEIC on a quarterly basis so that an accurate measurement of the amount of antibiotics used on a ’chicken medication day’ basis can be recorded and disseminated more widely as required. Our ambition is to be in a position where we can share data with the VMD in 2017 which will help confirm our belief that the egg sector is a low user of antibiotics.

Pigs

Contribution from the Pig Health and Welfare Council (PHWC) Antimicrobial Usage Sub-group:

The PHWC Antimicrobial Usage Sub‐group continues work to implement the action plan to promote the responsible use of antibiotics in UK pig production, which was developed from an industry wide workshop held in October 2014. In the last year, there has been significant progress in collecting data on antibiotic usage from UK pig farms following the launch by AHDB-Pork in April 2016 of an electronic medicines book (eMB-Pigs).

eMB-Pigs allows farmers to report antibiotic usage, monitor and benchmark their use with other farms and help them meet their obligations for antibiotic recording under farm quality assurance schemes. By the end of October 2016, 534 sites had signed up to eMB-Pigs, covering 17% of national pig production (2,544,186 finishers, 2,988,379 weaners and 371,580 sows and boars). AHDB-Pork are continuing to work with the large corporate pig producers, to encourage bulk data uploads to be provided, with feed companies, to encourage feed data to be uploaded directly into eMB-Pigs, and farm software companies, to promote data sharing. While it is still early days, and the data submitted need to be verified, it is hoped that 2016 aggregated, anonymised usage data will be included in the 2017 VARSS report.

In addition, and in conjunction with the subgroup, the Pig Veterinary Society (PVS) has produced guidelines for veterinary surgeons attending pigs on the need and procedure for regular clinical review of the use of antimicrobials in their clients’ pigs. The PVS has made the Society’s prescribing principles for antimicrobials available to all vets, not just PVS members, on their website. The National Pig Association (NPA) have also launched a Pig Industry Antibiotic Stewardship Programme in a bid to ensure and demonstrate responsible use of antibiotics in pigs, and have been working with PVS, AHDB-Pork, and the Veterinary Medicines Directorate, to progress its initiatives.

Chapter 2: Data Collection Activities to determine the level of Antibiotic Usage by Livestock Species

Cattle

Contribution from the Cattle Health and Welfare Group:

In 2014, the VMD commissioned the Cattle Health & Welfare Group (CHAWG) to undertake a scoping study to ascertain what antibiotic usage data are currently being collected and what should be done to develop data collection systems in the UK cattle sector (both dairy and beef). The 2015 study, and a follow up industry workshop in January 2016, concluded that there is a strong willingness to develop a robust and effective monitoring system but, although there are a number of individual initiatives, there is currently no central data collection point for the cattle industry.

A two stage process has been proposed, that will initially collects farm level dispensing and prescription data from veterinary practice records. This could then be followed by an industry agreed approach to collecting usage information directly from the farm. An industry working group, the Cattle Health and Welfare Group (CHAWG) Antimicrobial Usage Data Collection Steering Group, was established in June 2016 to agree on a way forward, and it is hoped that a system will be up and running by the end of 2017.

Future Plans

In the coming year the VMD’s focus will be to continue working with stakeholders to build on the activities and strategies outlined above, in particular increasing the number of farms using e-MB- Pigs and continuing to develop a data collection system for the cattle industry. Sector specific targets will also be developed, led by the industry, which will form the long-term, sustainable, evidence based basis for underpinning responsible use, and sharing examples of best practice in UK agriculture.

We will also continue to work with ESVAC on development of guidance on the type and format of antibiotic use data per species required and how to measure the total animal population at risk. This will allow collation, analysis and reporting harmonised and standardised data on population- corrected antibiotic use per species across European countries. The proposal will be available for public consultation on 15th December 2016, with a final version to be agreed by 30th April 2017.

Chapter 3: EU Harmonised Monitoring of Antibiotic Resistance

Introduction

EU harmonised monitoring of AMR is a programme set out in EU legislation which aims to evaluate antibiotic resistance in bacteria of relevance to human health which have been isolated from healthy animals. The sample size and sampling strategy have been designed to provide a representative sample which reflects the wider population

Susceptibilities are presented as human clinical break points (CBPs) in this report and epidemiological cut‐off values (ECVs).

 CBPs relate laboratory results to likely clinical treatment success or failure. Therefore, ‘resistant’ results using CBPs correspond to a likelihood of treatment failure when using an antibiotic to treat a clinical infection caused by that bacterial isolate.

 ECVs represent the point at which bacteria have developed a higher level of resistance to an antibiotic than the background level of resistance that exists naturally for that bacterial species. A ‘resistant’ (or ‘non‐susceptible’) ECV does not necessarily imply a level of resistance which would correspond with clinical treatment failure.

Susceptibilities interpreted using both ECVs and human CBPs are provided in full in the main body of the report, or in Annex 10.

Surveillance conducted in livestock under EU Harmonised Monitoring in 2015

The EU harmonised monitoring legislation (Commission Decision 2013/652/EU) ‘on the monitoring and reporting of antimicrobial resistance in zoonotic and commensal bacteria’ mandates all EU Member States to monitor AMR in specified bacteria in food producing animals at slaughter, and food products at retail. An overview of this sampling plan, by year, is summarised in Annex 6.

In 2015, Member States were mandated to carry out three sets of testing:

 Susceptibility testing of randomly selected Escherichia coli isolates obtained from the caecal contents of pigs at slaughter  Testing for the presence of Extended Spectrum -Lactamase (ESBL), AmpC, and carbapenemase producing E. coli in caecal contents of pigs at slaughter using selective media. The method screens large numbers of E. coli and can detect low numbers of resistant organisms.  Susceptibility testing of Salmonella isolates derived from pig carcass swabs taken by food business operators at the end of processing

Selection of isolates for susceptibility testing was based on the criteria laid down in EU technical specifications (Commission Decision 2007/516/EC). This protocol for testing E. coli from pigs was adopted for the first time in 2015; therefore only one year’s worth of E. coli resistance data are presented in this chapter.

The importance of these EU surveillance activities and the relevant legislation is three‐fold:

Chapter 3: EU Harmonised Monitoring of Antibiotic Resistance

 The organisms for which the legislation outlines monitoring provisions, such as Salmonella and E. coli, are of direct relevance to human health. Additionally, the panel of antibiotics against which these organisms must be tested has been selected based on relevance to human health and includes antibiotics, such as 3rd and 4th generation cephalosporins and fluoroquinolones that are defined by the WHO as the Highest Priority Critically Important Antibiotics (HP-CIA) for human health.  The legislation and accompanying technical specifications provide a standardised and harmonised sampling methodology which produce comparable and robust susceptibility data for a representative proportion of food producing animals and food products across the EU.  The legislation provides a harmonised set of ECVs and human CBPs to interpret susceptibility to antibiotics. This will enable the comparison of animal resistance data with similar data generated by human health, both within the UK and across the EU. MICs are also recorded, and will enable any future changes in ECVs or CBPs to be taken into account.

Method

In accordance with Commission Decision 2013/652/EU, 2007/516/EC, and the Microbiological Criteria for Foodstuffs, all of the required tests were conducted by the network of APHA veterinary laboratories located throughout Great Britain. A summary of the three required tests is provided:

 Caeca were collected randomly from healthy pigs at slaughter. E. coli were cultured from the caecal samples on non-selective agar, and then a single colony selected from each caecal sample for susceptibility testing against a defined panel of antibiotics using a standardised broth micro-dilution method. Resistance was determined using EUCAST CBPs (see Table 3.1 for results).  Caecal contents were also enriched and plated on to three types of selective agar (MacConkey + cefotaxime, ChromID OXA-48 and ChromID carba) to test for the presence of ESBL, AmpC and carbapenemase producing E. coli (see Table 3.2 for results).  Carcass swabs were collected by food business operators and then submitted to private laboratories for culture. Where a sample was found to be positive for Salmonella the private laboratory was asked to inform APHA and submit isolates for susceptibility testing and serotyping (see Figure 3.2 for results).

Chapter 3: EU Harmonised Monitoring of Antibiotic Resistance

Escherichia coli

In 2015, 150 E. coli isolates from pig caecal samples collected at slaughter throughout the year were tested for AMR. These E. coli were recovered from non-selective media and were randomly- selected. They are likely to represent those E. coli most frequently present in the samples, as those which occur more frequently are more likely to be selected when a single colony is chosen for susceptibility testing.

Figure 3.1: Percentage resistance (interpreted using EUCAST CBPs) in Escherichia coli isolates from pigs (n=150) in 2015

80 70 60 50 40 30 20 10 Percentage resistant Percentage 0 Colistin Ampicillin Tigecycline Cefotaxime Gentamicin Ceftazidime Meropenem Ciprofloxacin Nalidixic acid Tetracyclines Trimethoprim Chloramphenicol Antibiotic

Chapter 3: EU Harmonised Monitoring of Antibiotic Resistance

Table 3.1: Resistance in E. coli (interpreted using both CBPs and ECVs) from pig caecal samples in 2015

No. of isolates resistant (%) Antibiotic based on CBPs based on ECVs Ampicillin 57 (38%) 57 (38%) Azithromycin * * Cefotaxime 0 (0%) 0 (0%) Ceftazidime 0 (0%) 0 (0%) Chloramphenicol 48 (32%) 47 (31.3%) Ciprofloxacin 1 (1%) 4 (2.7%) Colistin 0 (0%) 0 (0%) Gentamicin 10 (6.6%) 11 (7.3%) Meropenem 0 (0%) 0 (0%) Nalidixic acid 2 (1.3%) 2 (1.3%) Sulphonamide * 87 (58%) Tetracyclines 108 (72%) 108 (72%) Tigecycline 0 (0%) 0 (0%) Trimethoprim 73 (48.6%) 73 (48.6%)

E. coli from pigs (n=150)

* = No EUCAST breakpoint available

Table 3.2: Results of specific testing for ESBL producing E. coli in pig caecal samples following selective culture in 2015

caecal samples yielding E. coli No. (%) MacConkey agar + 1 mg/L CTX * 81/327 (24.7) agar selective for carbapenemase producers (Chrom ID CARBA agar) ** 0/294 (0) agar selective for OXA-48 carbapenemase producers (Chrom ID OXA-48 agar) ** 0/294 (0)

*These samples originate from unique pig herds from across the UK

**These samples originate from unique pig herds from GB only

Table 3.2 summarises the numbers of samples cultured on each selective agar and the number from which E. coli with particular types of resistance were recovered. Whilst these selective methods are effective techniques for defining the presence or absence of ESBL, AmpC and carbapenemase producing E. coli in a sample, they do not enumerate or further characterise the E. coli present, and therefore are not able to quantify the risk which these bacteria may potentially pose to human or animal health. Selective methods are used to detect low numbers of resistant E. coli which may be present as a minor component of the total flora.

Chapter 3: EU Harmonised Monitoring of Antibiotic Resistance

APHA conducted a survey in 2013 to look for ESBL producing E. coli in pig caecal samples. A comparison of results and methods of the 2013 APHA survey and 2015 EU monitoring testing can be found in Annex 9.

Salmonella spp.

In 2015, a total of nine Salmonella isolates from pig carcass swab samples were examined for AMR (Fig. 3.2). As only a small number of isolates were recovered, the results are not likely to be representative and should be interpreted with caution.

Action has been taken to increase the number of samples received in future years. More details can be found in Annex 7.

Figure 3.2: Resistance (interpreted using EUCAST CBPs) in Salmonella spp. from pig carcass swab samples (n=9) in 2015

100 90 80 70 60 50 40 30 20 Percentage resistant Percentage 10 0 Colistin Ampicillin Tigecycline Cefotaxime Gentamicin Ceftazidime Meropenem Ciprofloxacin Nalidixic acid Tetracyclines Trimethoprim Chloramphenicol Antibiotic

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Introduction

Clinical surveillance is a programme of passive surveillance, which evaluates antibiotic resistance in bacteria of relevance to animal health which have been isolated from diagnostic samples submitted to APHA. The primary aim of this testing is as a diagnostic service for veterinarians. However, it also serves to identify rare and emerging patterns of resistance, particularly since treatment failure is a frequent reason for submission of material. Any findings that are considered to pose a potential risk to human or animal health are reported to the Defra Antimicrobial Resistance Coordination (DARC) group for consideration and management in accordance with the protocols outlined in the VMD AMR Contingency Plan: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/497125/771046_Cont ingency_planning_guidance.pdf

The results of this surveillance are compiled to provide an overview of the resistance observed in isolates associated with clinical infections in livestock. This programme relies on the submission of carcasses or other diagnostic samples by private veterinary surgeons APHA veterinary laboratories. These laboratories are situated in England and Wales, with the exception of APHA Lasswade, in Scotland. This chapter reports the APHA methods and results.

Similar programmes are conducted by Scottish (SAC Veterinary Services) and Northern Irish (Agri- Food Biosciences Institute) laboratories. The methods used are detailed in Annex 8 and Annex 18, and data relating to resistance in Salmonella and E. coli from Scotland and Northern Ireland are presented in Annexes 16 and 17. Where it is clinically relevant, culture and sensitivity testing is undertaken on isolates recovered from submitted samples. Since clinical surveillance is a passive form of surveillance, findings may not be representative of the wider population and therefore are not a prediction of prevalence.

Susceptibility testing methodology

Susceptibility tests were conducted by the network of APHA Veterinary Investigation Centres in England and Wales. For isolates recovered through the clinical surveillance scheme, the susceptibility tests described were performed (unless otherwise stated) using a disc diffusion technique on Isosensitest Agar (Oxoid) with appropriate media supplementation, where necessary, for fastidious organisms, using the method described by the British Society for Antimicrobial Chemotherapy (BSAC,2015).

The disc concentrations used are as stated in Annex 8. Resistance was interpreted using human CBPs as published by BSAC. Isolates have been classed as either sensitive or resistant; under the BSAC guidelines intermediate isolates are considered resistant. For some veterinary ‘drug/bug’ combinations there are no published BSAC breakpoints available. In these cases, a historical APHA veterinary breakpoint (13mm zone size diameter) has been used to indicate resistance.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Results

Where more than 20 isolates of any pathogen were recovered in any given year the results are presented graphically in the main body of the report, with additional numerical data available in the annex. Where fewer than 20 isolates were recovered, results are presented in the annex only.

Mastitis Pathogens

Escherichia coli: E. coli and other coliforms are one of the three main causes of bovine mastitis (resistance in E. coli isolates not associated with mastitis is reported in Table 4.2). Most strains originate from the immediate environment of the cow and it is thought that no special virulence factors are required to infect the mammary gland. These isolates therefore represent the normal types that are present in the environment of adult dairy cattle, particularly cattle sheds and cubicle houses, and are probably mainly of faecal origin.

Figure 4.1: Resistance and susceptibility (interpreted using BSAC CBPs) of E. coli isolates from mastitis infections of cattle, 2013-2015

180 2013 2014 2015 160

140

120

100

No. of isolates 60 Susceptible Resistant 40

0 Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Trim/Sulph Trim/Sulph Trim/Sulph Amoxi/Clav Amoxi/Clav Amoxi/Clav Tetracycline Tetracycline Tetracycline Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Cefpodoxime Cefpodoxime Cefpodoxime Antibiotic

Streptococcus dysgalactiae: S. dysgalactiae is a Lancefield Group C streptococcus and a commensal of the mucous membranes of cattle. It is a cause of mastitis and occasionally other diseases in other livestock species. It is not considered a zoonosis, because Group C streptococci that can cause disease in humans constitute a separate population.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.2: Resistance and susceptibility (interpreted using BSAC CBPs) of S. dysgalactiae isolates from mastitis infections of cattle, 2013-2015

50 2013 2014 2015

20 Susceptible Resistant

No. of isolates 10

0 Tylosin Tylosin Tylosin Penicillin Penicillin Penicillin Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Novobiocin Novobiocin Novobiocin Amoxi/Clav Amoxi/Clav Amoxi/Clav Tetracycline Tetracycline Tetracycline Antibiotic

Streptococcus uberis: S. uberis is widely distributed in the environment and a normal commensal resident of the bovine vagina, tonsil and skin. It is a common cause of mastitis and not regarded as zoonotic.

Figure 4.3: Resistance and susceptibility (interpreted using BSAC CBPs) of S. uberis isolates from mastitis infections of cattle, 2013-2015

130 2013 2014 2015 120 110 100 90 80 70 60 50

No. of isolates 40 Susceptible 30 Resistant 20 10 0 Tylosin Tylosin Tylosin Penicillin Penicillin Penicillin Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Novobiocin Novobiocin Novobiocin Amoxi/Clav Amoxi/Clav Amoxi/Clav Tetracycline Tetracycline Tetracycline Antibiotic

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Staphylococcus aureus: S. aureus is normally resident on the skin and mucous membranes of cattle and is a common cause of mastitis. It is not generally regarded as a common cause of zoonotic infections, and although both MRSA and a recently-described variant form of MRSA have been detected in cattle (Vanderhaeghen et al. 2010, García-Álvarez et al. 2011), the possible role of cattle as a source of human infection has not been well-defined. Other strains of S. aureus are, for the most part, generally specific to a host-species. S. aureus isolates from non-mastitis cases are detailed in Annex 15.

Figure 4.4: Resistance and susceptibility (interpreted using BSAC CBPs) of S. aureus isolates from mastitis infections of cattle, 2013-2015

120 2013 2014 2015 110 100 90 80 70 60 50

The most frequently isolated organisms from milk samples sent to APHA in 2015 were Streptococcus uberis, E. coli and Staphylococcus aureus. In general, streptococci are naturally resistant to aminoglycosides, therefore the finding that 79/119 (60%) of S. uberis isolates were resistant to neomycin is not unexpected. Tetracycline resistance was also common with 62/123 (50%) isolates being resistant. None of the authorised intramammary preparations contain tetracycline antibiotics so this high level of resistance is not likely not to be attributable to use of these preparations. S. uberis is ubiquitous in the environment and can exist in the gastrointestinal tract and on the skin of bovines. Without knowledge of the clinical history of each case, it is not possible to assess whether the tetracycline resistance may have been selected for by efforts to treat mastitis with systemic antibiotics, or as a result of the bacteria being exposed to systemic or oral antibiotics used in the treatment of other conditions.

Penicillin resistance in Staphylococcus aureus from mastitis cases is not a novel finding in the UK. However the finding that 25/77 (32%) of isolates were resistant to penicillin and amoxicillin and 12% were resistant to amoxicillin/clavulanic acid in 2015 is significant as many intramammary preparations contain these antibiotics. This highlights the need for regular and accurate culture and

Chapter 4: Clinical Surveillance of Antibiotic Resistance

sensitivity testing, as in one third of cases empirical treatment with penicillin may have resulted in treatment failure and prolonged disease.

Mastitis is complex and the patterns of resistance observed vary with time and between farms. These data are aggregated at a national level and therefore have a limited ability to inform treatment protocols, but they do highlight that acquired resistance does occur in England and Wales and this should be considered when vets and farmers develop mastitis control programs for individual farms.

Respiratory Pathogens

Cattle

Pasteurella multocida is a causative agent of respiratory or systemic disease in cattle. Toxigenic strains are responsible for the development of atrophic rhinitis in pigs and strains of the organism can also affect poultry (fowl cholera). It is a rare pathogen of sheep in the UK. There is probably carriage in the upper respiratory tract of some animals and bovine strains are likely to be distinct from those infecting other species.

Figure 4.5: Resistance and susceptibility (interpreted using BSAC CBPs) of P. multocida isolates from respiratory infections of cattle, 2013-2015

45 2013 2014 2015 40

No. of isolates Susceptible 15 Resistant 10

0 Ampicillin Ampicillin Ampicillin Florfenicol Florfenicol Florfenicol Amoxi/Clav Amoxi/Clav Amoxi/Clav Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Enrofloxacin Enrofloxacin Enrofloxacin Cefpodoxime Cefpodoxime Cefpodoxime Antibiotic

Chapter 4: Clinical Surveillance of Antibiotic Resistance

It is noteworthy that resistance to florfenicol was identified in 1/40 (3%) isolates of P. multocida from cattle in 2015 as it had not been identified in 2013 or 2014. Florfenicol is effective for treating a number of pathogens which contribute to bovine respiratory disease complex; therefore it is a valuable option for the treatment of the bacterial component of respiratory disease in cattle. At present it is not possible to estimate the prevalence or significance of this resistance in the bovine population. However, this finding, combined with the finding of quite high levels of tetracycline resistance, demonstrates that resistance is present and reinforces the need to reduce incidence of respiratory disease in cattle through measures such as improving biosecurity, optimising husbandry, and vaccination.

Sheep

Mannheimia haemolytica is a common cause of respiratory disease in the UK. There is carriage in the upper respiratory tract in healthy animals and ovine Mannheimia strains can also occasionally cause bovine mastitis. Further data on less frequently isolated ovine respiratory pathogens such as Bibersteinia trehalosi and Trueperella pyogenes can be found in Annex 12 and Annex 14.

Figure 4.6: Resistance and susceptibility (interpreted using BSAC CBPs) of M. haemolytica isolates from respiratory infections of sheep, 2013-2015

2013 2014 2015 35

15 No. of isolates Susceptible Resistant 10

Antibiotic

The number of M. haemolytica isolates cultured from sheep was low and therefore any trends need to be interpreted with caution. However, antibiotic resistance appears to be rare in these isolates and may reflect the suspected low use of antibiotics in sheep.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Other Animal Pathogens

Brachyspira hyodysenteriae: B. hyodysenteriae is the causative organism of swine dysentery, an enteric disease of pigs, resulting in serious ill-thrift in its chronic form. A limited range of antibiotics is available for the treatment of swine dysentery and, since resistance arises through mutation, reliance on on-going medication without addressing other aspects of disease control, such as hygiene and herd husbandry carries the attendant risk that mutational resistance may arise.

Tiamulin is an important antibiotic used for the treatment of swine dysentery. Tiamulin-resistant isolates are of particular concern as they may also show resistance to some or all of the other antibiotics currently used for treatment. When resistance occurs to all of the available therapeutic antibiotics then important animal welfare considerations arise. In such instances, the only practical option may eventually be to depopulate herds, with serious economic implications for the farmer. However, tiamulin-resistance in B. hyodysenteriae in conjunction with resistance to other available therapeutic compounds remains extremely uncommon. It should be noted that B. hyodysenteriae is not a zoonotic pathogen and tiamulin is not used to treat humans, therefore concerns about resistance in this pathogen are centred on animal health and welfare.

The susceptibility of selected B. hyodysenteriae isolates tested between 2010 and 2015 is shown in Figure 4.7; 51 isolates were recovered and tested during this period. This includes some “repeat” isolates (i.e. isolates recovered from the same farm premises over a period of time) and two isolates from 2013 taken from the same premises which had a tiamulin MIC>8mg/L. A breakpoint of resistance >4 mg/L tiamulin was used (Rønne and Szancer, 1990), which has also recently been quoted in a Dutch study of swine dysentery in pigs (Duinhof et al., 2008).

Figure 4.7: Resistance and susceptibility of Brachyspira hyodysenteriae isolates from pigs in England and Wales to tiamulin, 2010-2015

14 12 10

8 6 Susceptible 4 Resistant

No. of isolates 2 0 2010 2011 2012 2013 2014 2015 Tiamulin

Chapter 4: Clinical Surveillance of Antibiotic Resistance

In 2015, one of five B. hyodysenteriae isolates was resistant to tiamulin (Fig. 4.7). Because of the importance of this disease and the significance of resistance to tiamulin, all available isolates are tested for tiamulin susceptibility each year.

Zoonotic Pathogens

Streptococcus suis: S suis is a pathogen that can cause pneumonia, meningitis and arthritis in pigs. It can also rarely infect man. Between 2013 and 2015, 182 isolates were recovered from pigs via clinical surveillance activities (see Annex 15 for further information).

Figure 4.8: Resistance and susceptibility (interpreted using BSAC human clinical breakpoints) of S. suis isolates from pigs, 2013-2015

70 65 2013 2014 2015 60 55 50 45 40 35 30

No. of isolates 25 Susceptible 20 Resistant 15 10 5 0 Tylosin Tylosin Tylosin Penicillin Penicillin Penicillin Ampicillin Ampicillin Ampicillin Lincomycin Lincomycin Lincomycin Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Enrofloxacin Enrofloxacin Enrofloxacin Antibiotic

No resistance to ampicillin or penicillin was observed in S. suis in 2015. These antibiotics are often recommended for treatment of S. suis, so the absence of resistance is favourable. The findings suggest that treatment with highest priority critically important antibiotics were rarely indicated in these cases.

Each year a large proportion of S. suis isolates were resistant to tetracycline with 59/63 (94%) resistant in 2015, however tetracycline is not commonly used for the treatment of this disease. S. suis can reside in the tonsillar crypts of asymptomatic pigs, therefore the resistance observed may be a result of exposure following oral administration of tetracycline for the treatment of a different condition.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Livestock Associated-MRSA

LA-MRSA was detected for the first time in 2005, and has since spread worldwide, being detected in the UK for the first time in 2013.

LA-MRSA is different from other types of MRSA, such as hospital or community associated strains which are more frequently found in humans. Anyone who has contact with colonised livestock can become colonised with LA-MRSA but prolonged colonisation is more likely in people who have regular, prolonged contact with colonised animals. LA-MRSA usually lives in the nose or on skin but if it is able to get into the body e.g. via a wound it can cause an infection. Usually this is a local skin infection, but occasionally it can cause diseases such as pneumonia or blood stream infections.

Further information for people who work with livestock is available at https://www.gov.uk/government/publications/la-mrsa-information-for-people-who-work-with- livestock.

A summary of all findings identified by UK government veterinary laboratories is provided in Table 4.1. These reports should not be interpreted as a prediction of prevalence in the animal population, as samples have been collected through differing methods of passive surveillance in animals which are affected with clinical disease. Results may therefore not be representative of the wider, healthy population.

Table 4.1: Findings of LA-MRSA in the UK by government laboratories, 2013-2015

Country of isolation Year Clonal complex Animal species Source England & Wales 2013 CC398 Poultry Clinical investigation Northern Ireland 2014 CC398 Pig Clinical investigation England & Wales 2014 CC398 Pig Clinical investigation England & Wales 2015 CC398 Pig Research project Northern Ireland 2015 CC30 Pig Clinical investigation Northern Ireland 2015 CC398 Dairy cattle Clinical investigation Northern Ireland 2015 CC398 Pig Clinical investigation Northern Ireland 2015 CC398 Pig Clinical investigation

CC398 is the most common LA-MRSA CC group isolated from food-producing animal populations in the UK. All isolates are whole genome sequenced and shared with Public Health England (PHE) to investigate any possible associations with infections in humans.

Data for all Staphylococcus aureus isolated from clinical investigations in livestock can be found in Annex 15.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Escherichia coli

E. coli is an important ubiquitous bacterium with a zoonotic potential. E. coli can, however, occur as a commensal organism in animals and humans, and has the capacity to function as a reservoir of transferable resistance determinants.

This section of the report includes all isolates of E. coli and coliform bacteria presumptively identified as E. coli through clinical surveillance activities, with the exception of isolates recovered from milk which are included in a previous section on mastitis organisms.

The majority of isolates reported in this section were recovered from faeces or intestinal contents, and includes both pathogenic and commensal strains. Results have been collated for the major food‐producing animals (Table 4.2), and resistance data analysed to animal species and age category level (Fig.4.9 - 4.15).

Data from England and Wales are presented in the main body of the report. Data for Scotland and Northern Ireland are presented in Annex 16.

Table 4.2: Resistance in all Escherichia coli isolates from cattle, pigs, sheep, broilers and turkeys (all ages, combined) from 2013-2015

No. of isolates resistant / No. of isolates tested (% resistant) Antibiotic 2013 2014 2015 Amikacin 4/856 (0.5%) 2/590 (0.3%) 3/524 (0.6%) Amoxi/Clav 447/1296 (34.5%) 314/1045 (30%) 282/1034 (27.3%) Ampicillin 892/1400 (63.7%) 733/1144 (64.1%) 713/1101 (64.8%) Apramycin 85/1360 (6.3%) 73/1118 (6.5%) 60/1073 (5.6%) Cefotaxime 98/857 (11.4%) 80/593 (13.5%) 49/526 (9.3%) Cefpodoxime 27/434 (6.2%) 19/481 (4%) 34/474 (7.2%) Ceftazidime 53/857 (6.2%) 44/593 (7.4%) 34/526 (6.5%) Chloramphenicol 440/856 (51.4%) 298/590 (50.5%) 244/524 (46.6%) Doxycycline 86/371 (23.2%) 157/452 (34.7%) 132/451 (29.3%) Enrofloxacin 114/1400 (8.1%) 93/1144 (8.1%) 118/1101 (10.7%) Florfenicol 295/969 (30.4%) 209/764 (27.4%) 174/709 (24.5%) Neomycin 398/1282 (31%) 287/1049 (27.4%) 266/1030 (25.8%) Spectinomycin 565/1360 (41.5%) 441/1118 (39.4%) 462/1073 (43.1%) Streptomycin 556/933 (59.6%) 442/742 (59.6%) 443/685 (64.7%) Tetracycline 932/1400 (66.6%) 779/1144 (68.1%) 708/1101 (64.3%) Trimetho/Sulpho 508/1400 (36.3%) 442/1144 (38.6%) 420/1101 (38.1%)

Note: A table detailing the full breakdown of proportion of resistance to all antibiotics in all livestock species can be found in Annex 16.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Fluoroquinolones and 3rd/4th generation cephalosporins are considered to be highest priority critically important antibiotics (HP-CIA) for use in people (for more detailed discussion of this classification, please refer to Chapter 1). In general, the level of resistance to these antibiotics in E. coli isolates was low.

At the end of 2015 the EMA’s Antimicrobials Expert Group (AMEG) advised that colistin should also be considered as a HP-CIA. All clinical isolates are tested for resistance using a disc diffusion method; however colistin is a very large molecule which means that conventional disc diffusion is an unreliable method for testing colistin susceptibility. Following the recommendation by AMEG, APHA implemented a pre-diffusion method to test for colistin resistance. This additional step was adopted as standard in 2016 but was not frequently used in 2015; therefore results of colistin susceptibility testing in 2015 are not reported.

Resistance to the third generation cephalosporins (cefotaxime, ceftazidime or cefpodoxime) detected in E. coli/presumptive E. coli in animals will include resistance mediated by both ESBL and AmpC resistance mechanisms. The higher prevalence of resistance to cefotaxime versus ceftazidime observed, for example, in neonatal calves (Figure 4.10), may reflect the occurrence of ESBL enzymes which are cefotaximases, rather than ceftazidimases.

The relatively high frequency at which E. coli resistant to ampicillin are recovered from young calves may reflect the use of dry cow intra-mammary infusions in the dam and the transfer of residual antibiotics to calves in colostrum, which may then exert a selective pressure on the intestinal bacterial flora of the neonatal calf.

In general, lower levels of resistance to most antibiotics are consistently observed in sheep than in pigs and cattle. Cefotaxime and ceftazidime resistance were detected in neonatal lambs, the former at a slightly higher prevalence. As in calves, this may reflect the occurrence of ESBL enzymes which are cefotaximases, rather than ceftazidimases.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Plasmid mediated colistin resistance

In November 2015, the first report was published describing transferable resistance to colistin (Liu et al., 2015), mediated by the gene mcr-1, a key distinction to the known intrinsic resistance Colistin is a polymyxin antibiotic which has been used for many years to treat enteric infections (especially E. coli infections) in farm animals in many European countries. In the UK however, colistin has only been authorised for the treatment of animals since 2004. The emergence of resistant organisms in human medicine which are resistant to most or all other treatment options has meant that colistin, despite its toxicity when administered systemically, is increasing in importance as one of the antimicrobials of last resort for the treatment of pan-resistant Enterobacteriaceae (Klebsiella spp., E. coli), Pseudomonas spp. and Acinetobacter spp. infections in man. Human patients can be exposed to resistant bacteria from a number of different sources, including for example those occurring in healthcare settings, in international travellers, in domestically-produced and imported foodstuffs as well as in animals. Although resistant bacterial organisms can originate from a number of different sources, limiting the occurrence and diffusion of colistin resistance in bacteria in the animal population in the UK is desirable to minimise any exposure which might arise from that particular source.

A pig herd, in which phenotypic colistin resistance in E. coli had been detected, was already under active investigation in November 2015. This herd had been identified through scanning surveillance. The presence of mcr-1 conferring colistin resistance was subsequently confirmed in E. coli and Salmonella Typhimurium var. Copenhagen from the pig herd (Anjum et al. 2016).

The occurrence of mcr-1 within the UK pig population was subsequently assessed by screening 163 archived E. coli isolates from veterinary diagnostic submissions from pigs from England and Wales for the presence of mcr-1. The isolates originated from 105 different pig herds, collected in 2015/early 2016 and isolates from 2/105 different herds (1.9%) were positive for mcr-1. [This figure of two positive herds includes the herd referred to in the paragraph above].

Archived caecal samples from pigs, which had been stored frozen, were also examined for colistin resistance using a selective culture method. This involved culture in buffered peptone water and then plating onto MacConkey agar containing colistin and allowed only those isolates resistant to colistin (at the level of inclusion) to grow. The method therefore screened large numbers of different E. coli present in each caecal sample for resistance to colistin. The caecal samples each originated from different pig herds, which had been selected to ensure that they were from herds representative of the majority of pigs slaughtered in Great Britain. The transferable colistin resistance gene mcr-1 was detected in 2/313 pig caecal samples from different pig herds or 0.6%. These caecal samples had been anonymised as part of the abattoir surveillance protocol, so it is not known if these herds were related to those detected through surveillance of veterinary diagnostic submissions referred to in the paragraph above (Duggett et al 2016).

We now know that this type of transferable colistin resistance has been around for much longer than was first thought following studies in other countries, with reports of detection in archived bacteria from animals dating to 2005 in France and to the 1980s in China (Schwarz and Johnson, 2016). The European Medicines Agency recently considered the use of colistin in animals in the EU (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/07/WC500 211080.pdf); colistin consumption in animals in the UK currently lies below both the target and desirable levels for EU countries.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Cattle

For some livestock species, the age of the animal at the time of sampling can have a large impact on the percentage of resistant isolates detected, with a general trend towards decreasing resistance in adult livestock. Therefore, when interpreting the total resistance data presented in this section of the report, please note that large differences in the levels of resistance observed in the main livestock groups may reflect the differing proportions of the age‐classes of animals which have contributed to the figures.

Figure 4.9: Resistance (interpreted using BSAC CBPs) in E. coli from cattle (all ages) in 2013, 2014 and 2015

900 800 2013 2014 2015 700 600 500 400 300 Sensitive

No. of isolates tested No. of isolates 200 Resistant 100 0 Amikacin Amikacin Amikacin Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Florfenicol Florfenicol Florfenicol Apramycin Apramycin Apramycin Amoxi/Clav Amoxi/Clav Amoxi/Clav Cefotaxime Cefotaxime Cefotaxime Ceftazidime Ceftazidime Ceftazidime Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Spectinomycin Spectinomycin Spectinomycin Chloramphenicol Chloramphenicol Chloramphenicol

Antibiotic

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.10: Resistance (interpreted using BSAC CBPs) in E. coli in 2015 from cattle (by age category)

400 Neo-natal Pre-weaning Adult

350

300

250

200

150 Sensitive No. of isolates tested No. of isolates Resistant 100

0 Amikacin Amikacin Amikacin Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Florfenicol Florfenicol Florfenicol Apramycin Apramycin Apramycin Amoxi/Clav Cefotaxime Amoxi/Clav Cefotaxime Amoxi/Clav Cefotaxime Ceftazidime Ceftazidime Ceftazidime Tetracycline Tetracycline Tetracycline Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Spectinomycin Spectinomycin Spectinomycin Trimetho/Sulpho Trimetho/Sulpho Trimetho/Sulpho Chloramphenicol Chloramphenicol Chloramphenicol

Antibiotic

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Pigs

Figure 4.11: Resistance (interpreted using BSAC CBPs) in E. coli from pigs (all ages) in 2013, 2014 and 2015

200 2013 2014 2015 180

160

140

120

100

80 No. of isolates Sensitive 60 Resistant

0 Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Florfenicol Florfenicol Florfenicol Apramycin Apramycin Apramycin Amoxi/Clav Amoxi/Clav Amoxi/Clav Doxycycline Doxycycline Doxycycline Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Cefpodoxime Cefpodoxime Cefpodoxime Spectinomycin Spectinomycin Spectinomycin

Antibiotics

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.12: Resistance (interpreted using BSAC CBPs) in E. coli from pigs in 2015 (by age category) in 2015

120

Neo-natal Post-weaning Adult 100

40 Sensitive No. of isolates tested No. of isolates Resistant 20

0 Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Florfenicol Florfenicol Florfenicol Apramycin Apramycin Apramycin Amoxi/Clav Amoxi/Clav Amoxi/Clav Doxycycline Doxycycline Doxycycline Tetracycline Tetracycline Tetracycline Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Cefpodoxime Cefpodoxime Cefpodoxime Spectinomycin Spectinomycin Spectinomycin Trimetho/Sulpho Trimetho/Sulpho Trimetho/Sulpho Antibiotic

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.13: Resistance (interpreted using BSAC CBPs) in E. coli from sheep (all ages) in 2013, 2014 and 2015

250 2013 2014 2015 225

200

175

150

125

100 No. of isolates Sensitive 75 Resistant 50

0 Amikacin Amikacin Amikacin Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Florfenicol Florfenicol Florfenicol Apramycin Apramycin Apramycin Amoxi/Clav Cefotaxime Cefotaxime Amoxi/Clav Cefotaxime Amoxi/Clav Ceftazidime Ceftazidime Ceftazidime Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Spectinomycin Spectinomycin Spectinomycin Chloramphenicol Chloramphenicol Chloramphenicol

Antibiotics

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.14: Resistance (interpreted using BSAC CBPs) in E. coli from sheep in 2015 (by age category)

100 Neo-natal Pre-weaning Adult 90

30 Sensitive No. of isolates tested No. of isolates Resistant 20

0 Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Florfenicol Florfenicol Florfenicol Apramycin Apramycin Apramycin Cefotaxime Amoxi/Clav Cefotaxime Amoxi/Clav Cefotaxime Amoxi/Clav Ceftazidime Ceftazidime Ceftazidime Tetracycline Tetracycline Tetracycline Enrofloxacin Enrofloxacin Enrofloxacin Streptomycin Streptomycin Streptomycin Spectinomycin Spectinomycin Spectinomycin Trimetho/Sulpho Trimetho/Sulpho Trimetho/Sulpho Chloramphenicol Chloramphenicol Chloramphenicol

Antibiotics

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.15: Resistance (interpreted using BSAC CBPs) in E. coli from chickens in 2013, 2014 and 2015

325 300 2013 2014 2015 275 250 225 200 175 150 125 No. of isolates Sensitive 100 Resistant 75 50 25 0 Ampicillin Ampicillin Ampicillin Neomycin Neomycin Neomycin Apramycin Apramycin Apramycin Amoxi/Clav Amoxi/Clav Amoxi/Clav Doxycycline Doxycycline Doxycycline Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Tetracycline Trim/Sulpho Enrofloxacin Enrofloxacin Enrofloxacin Cefpodoxime Cefpodoxime Cefpodoxime Spectinomycin Spectinomycin Spectinomycin

Antibiotics

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Salmonella spp.

All Salmonella – Summary

This section of the report presents an overview of all the clinical surveillance of Salmonella isolates that were tested for resistance in 2013‐2015. Salmonella is also reportable under the Zoonoses Order 1989, so any laboratory which isolates Salmonella from a food producing animal is required to inform APHA and make the isolate available for further testing if requested, and as a result of this the clinical surveillance of Salmonella is enhanced. Salmonella originating from the National Control Programme for poultry in the UK were not susceptibility tested in 2015 and, as such, the dataset presented below does not include isolates from this source.

Due to the importance of Salmonella as a zoonotic pathogen, it is useful to look at the serotype and even phage type of an isolate when investigating potential epidemiological links between animal and human cases. For this reason, individual serotypes are also reported in this section. Considering the findings of this report in relation to Salmonella, resistance to third generation cephalosporins and fluoroquinolones is of particular importance, since these antibiotics are most commonly used for the treatment of human salmonellosis, where treatment is required. However it should be noted that most cases of non‐typhoidal Salmonella infection in humans are non‐invasive, limited to the gastro‐intestinal tract and do not require antibiotic treatment.

Where resistance to third generation cephalosporins and fluoroquinolones is detected in a food producing animal(s), attempts are made to visit the farms in order to explain the significance of the findings and provide appropriate advice on control. Only 0.9% of all Salmonella isolates were resistant to ciprofloxacin and 0.04% were resistant to ceftazidime or cefotaxime in 2015 (detailed below). Ciprofloxacin resistance was not detected in S. Typhimurium, one of the serotypes of particular public health importance.

Other noteworthy isolations in 2015 include:

 The isolation of S. Kentucky sequence type (ST) 198 with high-level fluoroquinolone resistance (MIC > 8mg/L) in a cattle herd in England and Wales. Salmonella Kentucky with these characteristics has been widely detected in North Africa and the Middle East, as well as in travellers to those areas, since 2000 and has subsequently been detected in poultry in some European countries. This isolation was the first report of the ST198 strain in livestock in Great Britain.

 Salmonella Typhimurium var Copenhagen with transferable colistin resistance (through possession of the mcr-1 gene) was identified on a pig farm in 2015.

 It should be highlighted that the number of cultures received from any one farm varies enormously, especially from poultry premises. Some poultry companies have a continuous monitoring programme in place and thus large numbers of Salmonella isolates may be received. In that situation, the numbers of isolates of a particular serotype and their antibiotic susceptibility may not reflect the prevalence in the animal population as a whole, but instead the intensity of the monitoring programme on a farm or group of farms. Therefore, to better indicate the prevalence of resistance, only the first isolate of a given serotype or phage definitive type (DT) from each incident has usually been tested.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

The Salmonella isolates reported in this section have been tested for their in vitro sensitivity to 16 antibiotics as defined in Annex 8. The choice of antibiotics, which is reviewed by APHA periodically, is designed to be a core set which are used in veterinary, as well as in human medicine:

 Amikacin  Ciprofloxacin  Neomycin  Ampicillin  Chloramphenicol  Streptomycin  Amoxicillin/Clavulanic acid  Gentamicin  Sulphonamide compounds  Apramycin  Furazolidone  Tetracycline  Cefotaxime  Nalidixic Acid  Trimethoprim/sulphonamide  Ceftazidime

Data from England & Wales are presented in the main body of the report. Additionally, data for Scotland and Northern Ireland are also presented in Annex 17.

Salmonella – By Animal Species

Figure 4.16 shows the number of Salmonella spp. isolates recovered from cattle, sheep, pigs, chickens and turkeys which were resistant to one or more antibiotics.

Figure 4.16: Percentage of Salmonella isolates from key animal species which were resistant to one or more antibiotics, 2013-2015

100 90 80 70 60 2013 50 2014 40 2015

more antibiotics 30 20 10

Percentage of isolates resistant to 1 or to resistant isolates of Percentage 0 Cattle Sheep Pigs Chickens Turkeys Animal species

Cattle – Of the 346 Salmonella recovered in 2015, the highest levels of resistance were seen to ampicillin (6.6%), streptomycin (5.8%), the sulphonamide compounds (5.2%) and tetracycline (6.1%). In all cases, this is a slight decrease on the levels seen in 2013. In 2015, 11.3% of all Salmonella isolates were resistant to one or more antibiotics. This is a slight increase compared to 2014 (11%) and 2013 (9.3%).

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Sheep – Of the 57 isolates cultured in 2015, the highest levels of resistance were observed to streptomycin (8.8%), sulphonamide compounds (7%), ampicillin (7%) and tetracycline (7%). In 2015, as in previous years, resistance in Salmonella from sheep was generally low, with 10.5% of all isolates resistant to one or more antibiotics tested. This is, however, an increase seen on the levels in 2014 (3.4%) and 2013 (5.5%).

Pigs – Of the 172 isolates recovered in 2015, 96.5% were resistant to one or more antibiotics tested. This is an increase on the levels seen in 2014 (81.4%) and 2013 (87.1%). A large proportion of isolates were resistant to streptomycin (90.1%) and the sulphonamide compounds (90.7%), an increase on the levels seen in 2014 (68.6% and 74.5%, respectively). Other notable resistances were observed to tetracycline (82.6%) and ampicillin (84.9% of isolates).

Chickens – Of the 768 isolates tested in 2015, the highest levels of resistance were seen to the sulphonamide compounds (20.6%) and tetracycline (16%), a slight increase on the levels seen in 2014. Resistance to the 3rd generation cephalosporins was absent and resistance to the fluoroquinolone ciprofloxacin was only seen in 0.7% (5/768) of isolates. Gentamicin resistance was observed in 2.3% of isolates, a slight decrease on the levels seen in 2014 (2.9%) and 2013 (3.5%). Of all Salmonella from chickens, 35.7% of isolates were resistant to one or more antibiotics tested, which is a similar level to previous years.

Turkeys – As with other livestock species, the highest levels of resistance in Salmonella from turkeys in 2015 (n=251) were seen to streptomycin (70.9%), sulphonamide compounds (75.3%) and tetracycline (73.3%), an increase of 5-11% on levels seen in 2014. Ninety-two percent of all isolates were resistant to one or more antibiotics tested, which is an increase on the levels seen in 2014 (86%) and 2013 (85.1%). Of all sources of Salmonella, ciprofloxacin resistance was the highest in isolates from turkeys (5.6%) in 2015, although this is a decrease on the levels seen in 2014 (11.2%) and 2013 (7%). Resistance to gentamicin was observed in 0.4% of isolates.

Top ten Salmonella serovars isolated between 2013-2015

Some serovars can have characteristic patterns of resistance, so knowledge of the most frequently isolated serovars can be of benefit when considering trends in resistance. The ‘top ten’ serotypes of non-typhoidal Salmonella isolates recovered from cattle, pigs, sheep, chickens and turkeys in England & Wales in 2013-2015 are presented in Figure 5.17. S. Dublin and S. Mbandaka are generally the most consistently isolated serovars year-on-year. Further details on the numbers of isolates can be found in Annex 17.

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Figure 4.17: The top ten most commonly isolated Salmonella serovars from livestock in 2013-2015

500

450

400

350

300 No. of isolates No. of isolates 250 Dublin Mbandaka Montevideo 200 Senftenberg Kedougou 150 13,23:i:- Typhimurium Ohio 100 Years Newport 50 Enteritidis 4,5,12:i:- 0 2013 4,12:i:- 2014 2015

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Salmonella Dublin

Of the 226 Salmonella Dublin cultures tested during 2015, 94.2% were susceptible to all 16 antibiotics (Table 4.3). The percentage of fully susceptible S. Dublin isolates has shown only slight fluctuations over the period 2005-2015 and the majority of isolates remain susceptible. This has been the situation since surveillance began in 1971.

Most S. Dublin isolates (92.9%) originated from cattle in 2015, and this was also similar to the situation recorded in previous years. Isolates from species other than cattle in 2015 were all fully susceptible to the panel of 16 antibiotics.

Of the 13 S. Dublin isolates showing antibiotic resistance in 2015, ten were only resistant to a single compound in the panel of antibiotics tested (neomycin (4), nalidixic acid (4), ampicillin (1), streptomycin (1).

Table 4.3: Resistance in Salmonella Dublin: percentage of resistant isolates in 2013, 2014 and 2015

Percentage of isolates resistant

2013 2014 2015 Antibiotic (n=393) (n=286) (n=226)

Ampicillin 0.3 0.7 1.8 Chloramphenicol 0.0 0.0 0.4 Furazolidone 0.0 0.3 0.0 Nalidixic Acid 1.0 0.0 2.2 Neomycin 0.3 0.3 2.2 Streptomycin 1.3 2.4 4.0 Sulphamethoxazole/Trimethoprim 0.0 0.7 0.0 Sulphonamide compounds 0.0 0.7 0.0 Tetracycline 0.0 0.3 0.4

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Salmonella Typhimurium

Forty-one percent of 165 isolates of S. Typhimurium examined in 2015 were sensitive to all of the antibiotics tested (Figure 4.18), which is a slight decrease compared to 44.2% in 2014, but an increase from 30.5% in 2013.

Between 2008 and 2014 the prevalence of resistance to sulphamethoxazole/trimethoprim has fluctuated between 26.4%-44.9%, and a level of 32.1% was seen in 2015. Isolates from pigs have predominantly accounted for these fluctuations as a high proportion of many definitive types of S. Typhimurium isolated from pigs are resistant to sulphamethoxazole/ trimethoprim.

No resistance to apramycin was detected in 2015. Apramycin resistance had increased for S. Typhimurium in 2011 and 2012 to 20.4%, a notable change when compared with preceding years, where apramycin resistance had been consistently less than 5%. More recently, apramycin resistance dropped to the low levels observed prior to 2011 (1.8% in 2013, 0.9% in 2014). Isolates resistant to apramycin were also resistant to gentamicin.

There were no isolates of S. Typhimurium resistant to ceftazidime, cefotaxime, ciprofloxacin, amoxicillin/clavulanate, furazolidone or amikacin recovered in 2015, The third generation cephalosporins and fluoroquinolones are often considered the first-line treatments for gram-negative invasive infections in man and might therefore be indicated for treatment of people with invasive or severe cases of Salmonellosis.

Figure 4.18: Salmonella Typhimurium: percentage of resistant isolates in 2013 (n=165), 2014 (n=224) and 2015 (n=165)

100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 2013 20.0 2014 10.0 2015 0.0 Percentage of isolates resistant isolates of Percentage Ampicillin Neomycin Apramycin Sulpha/Trim Tetracycline Furazolidone Streptomycin Naladixic Acid Chloramphenicol Antibiotic Sulpho compounds Sulpho

Chapter 4: Clinical Surveillance of Antibiotic Resistance

The eight most frequent definitive or undefined types subjected to susceptibility testing at APHA are given in Figure 4.19.

The generally high level of resistance of Salmonella Typhimurium isolates observed in recent years has partly been a reflection of the contribution of DT104 and its variants DT104B and U302, which have comprised more than a quarter of isolates in some years over the previous decade. Only 2.6% (1/39) of DT104 and U302 isolates were sensitive to all the antibiotics tested in 2015. No DT104B were isolated in 2015. The proportion of Salmonella Typhimurium isolates comprising DT104 and its variants has however declined significantly when a longer time period is considered. For further information on the phage types prior to 2015 please refer to the Salmonella in Livestock Production.

Figure 4.19: Number of isolates of Salmonella Typhimurium of the eight most frequent definitive or undefined types subject to susceptibility testing in 2015

n=7 U302 n=7 n=27 DT2 n=9 U288 n=12 DT193 DT104 n=25 n=19 DT1 DT40 DT8 n=24

Monophasic Salmonella Serotypes

Eighty-three isolates of the monophasic Salmonella 4,12:i:- were examined, belonging to phage types 120 (n=2), 193 (n=69), U302 (n=1) and U311 (n=2). Nine isolates were not typeable or reacted with phages but did not conform to a recognised phage type. Most isolates were from pigs (63.8%) with feed the next most common source of origin (9.6%). The most common pattern of resistance observed was to ampicillin, streptomycin, sulphonamide compounds and tetracycline (AmSSuT), occurring in 27/69 DT 193 isolates, 2/2 U311 isolates and 8/8 of the isolates which were not typeable with phages. 60/69 DT 193 isolates (86.9%) had the basic AmSSuT resistance pattern alone or with one or more additional resistances.

A total of 68 isolates of the monophasic Salmonella 4,5,12:i:- were examined, including phage types 191a (n=1), 193 (n=62), 29 (n=1), 8 (n=1), and U323 (n=1). One isolate was un-typeable and one isolate had no phage type information. The most common resistance pattern in DT 193 isolates was AmSSuT, occurring in 59.6% of isolates (37/62). Most isolates of DT 193 were from pigs (66.1%).

Chapter 4: Clinical Surveillance of Antibiotic Resistance

Salmonella other than Dublin or Typhimurium

Of the 2,198 isolates of serotypes other than S. Dublin and S. Typhimurium tested in 2015, 60.2% were sensitive to all the antibiotics in the panel, a decrease on the figure for 2014, when 68.2% were fully sensitive. One hundred and thirty-three (6.0%) of these isolates were S. Enteritidis of which 97/133 (72.9%) were fully susceptible. Resistance to one or more antibiotics was detected in S. Enteritidis isolates belonging to phage types 21, 35, 4, 4b, 8, 9b. No resistance was detected in isolates belonging to phage type 1, 11, 14b, 21b, 3, 33, 6a or 9a.

Neomycin resistant isolates originated mainly from chickens (761 isolates; 3.7% resistant), ducks (191 isolates; 7.8% resistant) and pigs (120 isolates; 8.3% resistant). The majority of the neomycin- resistant isolates from chickens were Salmonella Ohio (the same situation prevailed in 2011 - 2014). In ducks, S. Indiana was the main serotype showing resistance to neomycin (11/68 isolates resistant). The S. Indiana isolates from ducks were also frequently resistant to furazolidone (18/68 isolates).

The apparent increase in the prevalence of resistance to streptomycin, sulphonamides and tetracyclines which was observed following 2009 reflected in part the increased monitoring of turkeys that has occurred in between 2010 and 2013 under the Control of Salmonella in Turkeys Order. When looking at Salmonella isolates other than Typhimurium and Dublin from turkeys in 2015 (n=250), 71.2% were resistant to streptomycin, 75.6% to sulphonamides and 73.6% to tetracyclines. This is lower than the equivalent figures for pigs in 2014 (78-89%), but higher than those for chickens (15-20%) and cattle (7-9%).

Figure 4.20: Salmonella other than Dublin and Typhimurium, percentage of isolates resistant to antibiotics tested in 2013 (n=2328), 2014 (n=1837) and 2015 (n=2198)

100.0

80.0

60.0

40.0

2013 20.0 2014

Percentage of isolates resistant isolates of Percentage 2015

0.0 Ampicillin Neomycin Apramycin Sulpha/Trim Tetracycline Furazolidone Streptomycin Naladixic Acid Chloramphenicol Sulpho compounds Sulpho Antibiotic

References

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Annexes

Annex 1: Changes in Methodology

The European Commission (EC) has requested the European Medicines Agency (EMA) to take the lead in collating data collected on the use of antibiotic agents in animals in the European Union. The EMA has therefore developed a harmonised approach for the collection and reporting of data based on national sales figures. This is designed to be comparable with usage data of human antibiotics.

Published ESVAC reports are available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing _000302.jsp

The ESVAC publications use a different method to calculate mg/PCU compared to the approach previously used in the UK. Table A1.1 summarises these differences, which are also highlighted in Figure A1.2 and Table A1.2.

Table A1.1: Differences between the ESVAC and VARSS methodology used in previous publications for the calculation of quantity of antibiotic sold

UK-VARSS ESVAC

All authorised veterinary Topical presentations are not Products included antibiotic products. included.

Ingredients are converted to Active ingredient weights relate Calculation of active active moiety (the active directly to information held ingredient quantity molecule not including salts) within the SPC

Horses not included as food Horses included as food Calculation of PCU producing animals producing animals

Only takes into account All formulations (for all species) products which are authorised other than tablets included; it is Calculation of for use in food producing considered that tablets are mg/PCU animals only. Horses are primarily used in the treatment excluded. Takes into account of non-food producing animals. all administration routes.

Conclusion Likely underestimates mg/PCU Likely overestimates mg/PCU

Key:

= Increases overall mg/PCU = Decreases overall mg/PCU

Annexes

In order to harmonise the national and European reporting, the ESVAC methodology has been adopted in the current UK- VARSS report for the first time. The historical data based on the traditional UK methodology, as well as 2015 data calculated in the same way, can be seen in Figure A1.1.

Data have been collected from Market Authorisation Holders since 1993, although this was only a statutory requirement from 2005. Data shown in Figure A1.1 represent sales of antibiotics for therapeutic use only, and do not contain sales of products marketed as growth promoters, which were banned in 2006.

Figure A1.1: Tonnes of active ingredient of antibiotic sold for all species 1993-2015 using the original UK-VARSS methodology

Linear (Tonnes Sold) 600

500

400

300

200 Tonnes Active Ingredient Active Tonnes

100

0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Tonnes Sold 392 445 486 533 495 433 383 465 432 439 435 453 446 405 383 387 402 447 346 445 420 429 388

Annexes

ESVAC Method Original VARSS Method 70

Active Ingredient (mg / PCU) / (mg Ingredient Active 10

0 2011 2012 2013 2014 2015 ESVAC Method 51 66 62 62 56 Original VARSS Method 46 60 55 57 50

2011 2012 2013 2014 2015

VARSS ESVAC VARSS ESVAC VARSS ESVAC VARSS ESVAC VARSS ESVAC Tonnes of active 290 344 381 447 355 422 369 430 330 392 ingredient PCU 6330 6724 6354 6749 6404 6799 6518 6915 6584 6961 mg/PCU 46 51 60 66 55 62 57 62 50 56

Annexes

Figure A1.3 shows historical data for mg/PCU for 2005-2015, calculated using ESVAC methodology. The data represented accounts for sales of antibiotics for food producing animals only, inclusive of horses.

Figure A1.3: Milligrams (mg) of active ingredient of antibiotic sold for food producing species per Population Correction Unit (PCU) 2005-2015 using the ESVAC methodology

80 72 68 68 70 66 65 64 63 62 62 60 56

51 50

20 Active ingredient (mg/PCU) ingredient Active

0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Table A1.3 shows the sales for other antibiotic products, which include topical preparations and those for sensory organs e.g. aerosols, creams, gels, shampoos and ear and eye medications (not included in ESVAC calculation).

Table A1.3: Tonnes of active ingredient of antibiotic sold for all species by “other” routes of administration 2011-2015

2011 2012 2013 2014 2015 Others 2 2 2 3 2

Annexes

Annex 2: European Population Correction Unit (PCU)

When assessing antibiotic sales it is important that the demographics of the animal population potentially exposed to treatment are also taken into account, (see Annex 19 - data limitations). Table A2.1 shows the living population of UK food-producing animals recorded each year in Defra’s June Census for each of the last five reporting years. All figures are quoted in thousands of individual animals and are not adjusted to take into account seasonality or animals whose lives are shorter than a year.

Table A2.1: Number of livestock (in thousands) by food producing species 2011-2015

2011 2012 2013 2014 2015* Cattle 9933 9900 9844 9837 9919 Pigs 4441 4481 4885 4815 4739 Sheep 31634 32215 32856 32856 33337 Poultry** 162551 160061 162609 162609 167579

* 2015 Data are provisional as they have not been fully validated at the time of printing **Census data are an underestimate of the poultry population

In addition, census data do not take into account the weight of each particular species at the time of treatment with antibiotics. This is achieved through use of the PCU, a technical unit of measurement (where 1 PCU = 1kg of animal treated), which is calculated by multiplying a standardised average weight at time of treatment (see Table A1.3) with the associated annual animal/ slaughter numbers. The calculation also takes into account animals exported from the UK for slaughter, or imported to the UK for fattening. Full details on the methodology of calculation of the PCU can be found in the 2009 ESVAC report.

Table A2.2 shows the calculated combined UK PCU value for food producing species and horses. The standard formula used for calculation of the PCU for poultry does not include population figures for egg producers (laying hens) so the poultry PCU is an underestimate (EMA, 2011).

Annexes

Table A2.2: Population correction unit (PCU) (in thousand tonnes) by food producing species and total 2011-2015

2011 2012 2013 2014 2015 Total food producing 6724 6749 6799 6915 6961 species + horses* Sheep and goat 2661 2697 2760 2809 2795 Cattle 1767 1708 1692 1731 1743 Poultry 1012 1040 1059 1042 1082 Pig 717 733 716 745 770 Horses** 395 395 395 395 378 Fish 172 176 177 193 ***

* Total food producing species PCU includes cattle, pigs, sheep, goats, poultry (broilers), fish and horses. ** Horse population data are obtained from the British Equestrian Trade Association survey which is run every 5 years. *** UK aquaculture population statistics for 2015 are not yet available as they are collated through 2016. Therefore, for fish PCU calculation purposes, 2014 data have been used.

Companion animals are not included in the PCU as reliable population data cannot be collected and no agreed weights at time of treatment have been allocated for these species.

Annexes

Table A2.3: Average weights at time of treatment (kg) used to calculate the Population Correction Unit (PCU)

Average weight at Animal Category Source treatment (kg) Cattle Slaughter cows 425 Montforts (1999)1 Slaughter heifers 200 EMA2 Slaughter bullocks and bulls 425 Montforts (1999)1 Slaughter calves and young cattle 140 Montforts (1999)1; EMA2 Imported/ exported cattle for slaughter 425 Montforts (1999)1 Imported/ exported cattle for fattening 140 Montforts (1999)1 Livestock dairy cows 425 Montforts (1999)1; EMA2 Pigs Slaughter pigs 65 Montforts (1999)1 Imported/ exported pigs for slaughter 65 Montforts (1999)1 Imported/ exported pigs for fattening 25 M. Goll (Eurostat, personal comm.) Livestock sows 240 Montforts (1999)1 Poultry Slaughter broilers 1 Montforts (1999)1; EMA2 Slaughter turkeys 6.5 Montforts (1999)1; EMA2 Imported/ exported poultry for slaughter 1 Montforts (1999)1; EMA2 Sheep and goats Slaughter sheep and goats 20 Montforts (1999)1 Imported/ exported sheep and goats for 20 Montforts (1999)1 slaughter Livestock sheep 75 Montforts (1999)1 Horses Living horses 400 Montforts (1999)1; EMA2 Fish5 Rabbits Slaughter rabbits 1.4 EMA2

1 M.H.M.M. Montforts 1999. Environmental risk assessment for veterinary medicinal products. Part 1. Other than GMO- containing and immunological products. First update. 2 European Medicines Agency (EMA). Revised guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL 38 (EMEA/CVMP/ERA/418282/2005-Rev.1). 3 Assume broilers. 4 Assume lambs. 5 Data form Eurostat is given as 1,000 tonnes slaughtered fish (as live weight).

Annexes

Annex 3: Antibiotic Active Ingredients Authorised for Use in Animals

Class/Active Ingredient Authorised Species Tetracyclines Chlortetracycline Cattle, Pigs, Sheep, Chickens, Turkey, Ducks Doxycycline Pigs, Chickens, Turkey, Cats, Dogs, Pigeons Oxytetracycline Cattle, Pigs, Sheep, Chickens, Salmon, Trout, Dogs, Cats, Horses Tetracycline Cattle, Pigs, Chickens Potentiated Sulphonamides Sulfadiazine Cattle, Pigs, Chickens, Turkey, Cats, Dogs, Horses Sulfadimethoxine Pigeons Sulfadimidine Cattle, Pigs, Sheep Sulfadoxine Cattle, Horses Sulfamethoxazole Pigs, Chickens Trimethoprim Cattle, Pigs, Chickens, Turkey, Cats, Dogs, Horses Beta-lactams 1st Generation Cephalosporins Cefalexin Cattle, Cats, Dogs Cefalonium Cattle Cefapirin Cattle 3rd Generation Cephalosporins* Cefoperazone Cattle Cefovecin Cats, Dogs Ceftiofur Cattle, Pigs, Horses 4th Generation Cephalosporins* Cefquinome Cattle, Pigs, Horses Penicillins Cattle, Pigs, Sheep, Chickens, Turkey, Ducks, Salmon, Cats, Dogs, Amoxicillin Pigeons Ampicillin Cattle, Pigs, Sheep, Cats, Dogs Benzylpenicillin Cattle, Pigs, Sheep, Chickens, Cats, Dogs, Horses Cloxacillin Cattle, Sheep, Cats, Dogs, Horses Nafcillin Cattle Phenoxymethylpenicillin Pigs Aminoglycosides Apramycin Cattle, Pigs, Chickens Dihydrostreptomycin Cattle, Pigs, Sheep, Cats, Dogs, Horses Framycetin Cattle, Cats, Dogs Gentamicin Cats, Dogs, Horses, Rabbits Kanamycin Cattle

Annexes

Neomycin Cattle, Sheep, Cats, Dogs, Horses Spectinomycin Cattle, Pigs, Sheep, Chickens Streptomycin Cattle, Sheep, Cats, Dogs, Horses Fluoroquinolones* Danofloxacin Cattle, Pigs Difloxacin Cattle, Chickens, Turkeys, Dogs Cattle, Pigs, Sheep, Chickens, Turkeys, Goats, Cats, Dogs, Enrofloxacin Rabbits, Reptiles, Ornamental Birds, Rodents Marbofloxacin Cattle, Pigs, Cats, Dogs Orbifloxacin Dogs Pradofloxacin Cats, Dogs Macrolides Erythromycin Chickens Gamithromycin Cattle Spiramycin Cattle, Dogs, Cats Tildipirosin Cattle, Pigs Tilmicosin Cattle, Pigs, Sheep, Chickens, Turkey, Rabbits Tulathromycin Cattle, Pigs Tylosin Cattle, Pigs, Chickens, Turkey Tylvalosin Pigs, Chickens, Turkey, Game Birds Other Amphenicols Florfenicol Cattle, Pigs, Sheep, Salmon Lincomycins Lincomycin Cattle, Pigs, Chicken, Cats, Dogs Clindamycin Cats, Dogs Pirlimycin Cattle Pleuromutilins Tiamulin Pigs, Chickens, Turkey, Rabbits Valnemulin Pigs, Rabbits Polymixins Colistin Cattle, Pigs, Sheep, Chickens Polymixin B Cats, Dogs Steroidal antibiotics Fusidic acid Cats, Dogs, Rabbits

*denotes the classes of antibiotics which are considered ‘highest priority critically important antibiotics for people’ (HP- CIAs) based on classification by European Medicines ad hoc expert group on AMR.

Non- food producing species are indicated in italics

Annexes

Annex 4: Antibiotic Usage Data from British Poultry Council

In 2015, the British Poultry Council (BPC) reported the use of 46.18 tonnes of antibiotic active ingredient. This represents a reduction of 27% (17.28 tonnes) between 2014 and 2015, whereas the poultry population has remained steady (see Annex 2). This is the lowest reported value over the four years that BPC have been collecting these data, as demonstrated in Figure A4.1. Peak use was recorded in 2013, and BPC have indicated that this may have been associated with poor feed quality that year. Feed quality can significantly impact the intestinal health of the birds and is dependent on weather conditions during the growing and harvest period.

When looking specifically at chickens and turkeys reared for meat production, 43.18 tonnes of antibiotics were administered, which represents 44 mg/PCU. The PCU was calculated by using 90% of the national statistics (given that members of the BPC Antibiotic Stewardship Scheme represent approximately 90% of the UK poultry meat production).

Figure A4.1: Tonnes of active ingredient of antibiotic used by all members of the BPC Antibiotic Stewardship Scheme 2012-2015

100.00 90.00 80.00 70.00 60.00

50.00 40.00 30.00

Active Ingredient (tonnes) Ingredient Active 20.00 10.00

0.00 2012 2013 2014 2015

As highlighted in Figure A4.2 and Table A4.1, the decline in use in meat poultry species will have contributed to the 10% decline (40 tonnes) in the sales of antibiotic products authorised for farmed food producing species only and the 10% decline (28 tonnes) in the sales of antibiotic products authorised for use in poultry only + both pigs and poultry only between 2014 and 2015.

Annexes

Figure A4.2: Tonnes of active ingredient of antibiotic sold indicated for use in all farmed food producing species only, indicated for use in poultry only + both pigs and poultry only* and used by members of the BPC Antibiotic Stewardship Scheme 2012-2015

SalesSales - indicated – indicated for all for farmed use in food all farmed producing food species producing

SalesSales - indicated – indicated for poultry for use only in p+oultr pigsy and onl ypoultry + both pigs and poultry

UseUse - members – members of the of BPCthe BPC Antibiotic Antibiotic Stewarship Stewardshi Schemep Scheme 450

400

350

300

250

200

150

100 Active Ingredient (tonnes) Ingredient Active 50

0 2012 2013 2014 2015

* Does not include products indicated for use only in pigs

It is important to note the limitations when comparing this sales and use data. For example, some products licensed for poultry and both pigs and poultry may be used off license via the cascade in other species, and (unlike the BPC data) the poultry only + both pigs and poultry only sales data excludes products licensed for poultry +/- pigs alongside other species. Similarly, the BPC data also include products which are used off-label via the cascade within scope. These data are presented together to demonstrate the overall trend.

Annexes

Table A4.1: Tonnes of active ingredient of antibiotic sold indicated for use in all farmed food producing species only, indicated for use in poultry only + both pigs and poultry only* and used by members of the BPC Antibiotic Stewardship Scheme 2012-2015*

2012 2013 2014 2015 Sales – indicated for all farmed 396 368 383 343 food producing species only Sales – indicated for poultry only + 282 260 278 250 both pigs and poultry only* Use – members of the BPC 81.67 94.58 63.46 46.18 Antibiotic Stewardship Scheme**

* Does not include products indicated for use only in pigs **The figures are slightly adjusted from last year due to additional data being provided

Figure A4.3 shows that, when looking at antibiotic class, 93% were in the form of tetracyclines, amoxicillin and lincomycins.

Figure A4.3: Percentage of active ingredient of antibiotic used by members of the BPC Antibiotic Stewardship Scheme by class 2015

Potentiated Fluroquinolones Other sulphonamides 1% 2% 2%

Macrolides 2%

Lincomycins 11%

Tetracycline 52% Amoxicillin 30%

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Table A4.2: Tonnes of active ingredient of antibiotic used by members of the BPC Antibiotic Stewardship Scheme by class 2015

Tonnes Percentage Tetracycline 23.90 52 Amoxicillin 13.99 30 Lincomycins 4.81 11 Macrolides 1.06 2 Potentiated sulphonamides 1.00 2 Fluoroquinolones** 0.54 1 Other* 0.88 2 Colistin** 0.04

* includes aminoglycosides, penicillin, pleuromutalin, colistin and products under the cascade ** highest priority critically important antibiotics

When looking at the highest priority critically important antibiotics, fluoroquinolones account for 1% of the volume of antibiotics used and Figure A4.4 shows that this dropped by over 50% between 2014 and 2015. In addition, 3rd and 4th generation cephalosporins are not used by the industry and the use of colistin (which was very low) has now been stopped by the BPC in its flocks.

Figure A4.4: Tonnes of active ingredient of fluoroquinolones used by members of the BPC Antibiotic Stewardship Scheme 2014-2015

1.2

0.8

0.6

0.4

0.2 Active ingredient (tonnes) ingredient Active 0 2014 2015

In conclusion, the reductions in overall antibiotic use over the last 2 years and the reductions in fluoroquinolone use between 2014 and 2015 are highly commendable. This is likely to have been driven by the BPC’s Antibiotic Stewardship Scheme (as highlighted in chapter 2), a programme of work designed to promote the responsible use of antibiotics and reduce the use of antibiotics classed as the most highly critical for human health.

Annexes

Annex 5: Cascade Prescribing

The Cascade is a legislative provision in the Veterinary Medicines Regulations that allows a veterinary surgeon to prescribe unauthorised medicines that would not otherwise be permitted e.g. imported medicines or a medicine licensed for another species or human use. The principle of the Cascade is that, if there is no suitable veterinary medicine authorised in the UK to treat a condition, the veterinary surgeon responsible for the animal may in particular circumstances (for example to avoid causing unacceptable suffering) treat with an unauthorised medicine. Food producing animals may only be treated under the Cascade with medicines whose pharmacologically active substances are listed in the Table of Allowed Substances in Commission Regulation EU No 37/2010.

The data used in this report do not include data on sales of imported or human antibiotics used in animals in accordance with the prescribing cascade, as currently there is no mechanism by which such information can be obtained. The understanding is that use of human products in food producing species is not extensive, due to issues with longer withdrawal periods when using such products.

The VMD continues to explore methods that can accurately incorporate information on the amounts of antibiotics imported into/exported from the UK and methods that can accurately incorporate sales of antibiotics licensed for humans that are sold for animal use under the Cascade prescribing system.

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Annex 6: Summary of the EU Harmonised Monitoring Requirements of 2013/652/EU

Sampling Year 2014 2015 2016 2017 2018 2019 2020 Salmonella spp. - broilers x x x x Salmonella spp. - layers x x x x Salmonella spp. - fattening turkeys x x x x Salmonella spp. - broiler carcases x x x x Salmonella spp. - fattening turkey carcases x x x x Salmonella spp. - pig carcases x x x Campylobacter jejuni - broilers x x x x Campylobacter jejuni - fattening turkeys x x x x E. coli - broiler caeca x x x x E. coli - turkey caeca x x x x E. coli - pig caeca x x x ESBL, AmpC or carbapenemase producing E. x x x x coli - broiler caeca ESBL, AmpC or carbapenemase producing E. x x x x coli - turkey caeca ESBL, AmpC or carbapenemase producing E. x x x coli - pig caeca ESBL, AmpC or carbapenemase producing E. coli - fresh broiler meat, pig meat and bovine x x x x x x x meat gathered at retail Campylobacter coli - broilers x x x x Campylobacter coli - pigs x x x E. faecium and E. faecalis - broilers, fattening x x x x x x x turkeys, fattening pigs, bovines <1yr age

Key: Note: The UK is exempt from the monitoring of resistance in isolates of bovine origin as we do not meet the cattle (<1 year of age) slaughter throughput as specified in the legislation. x = Mandatory x = Voluntary

Pig and Bovine Poultry

Annexes

Annex 7: Sources of the bacteria to meet the EU Harmonised Monitoring Requirements of 2013/652/EU

Escherichia coli

Monitoring of antibiotic resistance in indicator E. coli recovered from healthy pigs in 2015 was based on the EU technical specifications in Commission Decision 2013/652/EU.

These E. coli were isolated from caecal samples collected at slaughter from UK pigs (January 2015 – December 2015). In accordance with the sampling framework as specified in the legislation, each isolate taken forward for resistance testing originated from a different herd of pigs.

These results were submitted to EFSA and are expected to be published in the EU Summary Report on Antimicrobial Resistance for 2015 (EFSA and ECDC, in preparation).

Salmonella spp.

Salmonella spp. isolates were recovered by Food Business Operators from pig carcase swab samples collected under Regulation 2073/2005, the microbiological criteria for foodstuffs. These samples were submitted by private laboratories to APHA, and one isolate per farm was taken forward for susceptibility testing.

The Food Standards Agency is the Competent Authority responsible for collating results on the number of samples collected under the Regulation 2073/2005 which are positive for Salmonella.

The low number of Salmonella received through this scheme is partly a reflection on the presence of Salmonella on pig carcases at slaughter, but it is also a reflection on the methodology used for sample collection and processing. In future years we will be working with colleagues in APHA and FSA to strengthen the robustness of this form of surveillance.

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Annex 8: Disc diffusion breakpoints, corresponding MIC breakpoints and breakpoints under review for the clinical surveillance isolates included in this report

Pasteurella, Disc charge Escherichia coli, Mannheimia, Antibiotic Salmonella Staphylococci Streptococci (micrograms) Enterobacteriaceae Histophilus, Actinobacillus R < 18mm R < 18mm Amikacin (AK) 30 NA NA NA R > 16mg/l R > 16mg/l Amoxicillin/ clavulanic R < 14mm R < 14mm 20/10 NA NA R < 13mm acid (AMC) R > 8mg/l R > 8mg/l Amoxicillin/ clavulanic R < 17mm 2/1 NA NA R < 13mm NA acid R > 1mg/l R < 14mm R < 14mm R < 29mm Ampicillin (AM) 10 R < 13mm R < 13mm R > 8mg/l R > 8mg/l R > 1mg/l R < 13mm R < 13mm Apramycin (APR) 15 NA NA R < 13mm† R > 32 mg/l R > 32 mg/l R < 29mm R < 29mm Cefotaxime (CTX) 30 NA NA NA R > 2mg/l R > 2mg/l R < 19mm Cefpodoxime 10 NA NA NA R < 13mm R > 1mg/l R < 26mm R < 26mm Ceftazidime (CAZ) 30 NA NA NA R > 2mg/l R > 2mg/l R < 15mm R < 24mm Cefalexin 30 NA R < 13mm R < 13mm R > 16mg/l R > 2mg/l R < 20mm R < 20mm Chloramphenicol (C) 30 NA NA NA R > 8mg/l R > 8mg/l R < 16mm Ciprofloxacin (CIP) 1 NA NA NA NA R > 1mg/l

Annexes

R < 30mm Doxycycline 30 R < 13mm NA NA R < 13mm R > 2mg/l R < 19mm R < 21mm* Erythromycin 5 NA NA R < 13mm R > 2mg/l R > 0.5mg/l R < 13mm Enrofloxacin 5 NA R < 13mm R < 13mm R < 13mm R > 4mg/l R < 13mm Florfenicol 30 NA NA R < 13mm R < 13mm R > 32mg/l

Furazolidone (FR) 15 NA ≤13mm NA NA NA

R < 19mm Gentamicin (CN) 10 NA NA NA NA R > 4mg/l

Lincomycin 10 NA NA R < 13mm R < 13mm R < 13mm

Nalidixic acid (NA) NA NA < 13mm NA NA NA

R < 13mm R < 13mm Neomycin (N) 10 NA NA NA R > 8mg/l R > 8mg/l

Neomycin 30 NA NA R < 13mm R < 13mm NA

Novobiocin 30 NA NA R < 13mm R < 13mm NA

R < 24mm R < 19mm** R < 21mm Penicillin 1IU NA NA R > 0.12mg/l R > 0.25mg/l R > 0.12 mg/l

Spectinomycin 25 R < 13mm NA NA NA R < 13mm†

R < 12mm R < 13mm Streptomycin (S) 10 NA NA R < 13mm† R > 8mg/l R > ~8mg/l Sulphonamide 300 NA < 13mm NA NA NA compounds (SU)

Annexes

R < 13mm R < 13mm R < 19mm R < 19mm*** Tetracycline (T) 10 R < 25mm R > 8mg/l R > 8mg/l R > 2mg/l R > 2mg/l Trimethoprim/ R < 15mm R < 15mm R < 16mm R < 19mm 25 R < 13mm sulphonamide (TM) R > 4mg/l R > 4mg/l R > 4mg/l R > 2mg/l

Tylosin 30 NA NA R < 13mm R < 13mm R < 13mm

Key:

BSAC human clinical breakpoint

Animal and Plant Health Agency (APHA) historical veterinary disc diffusion zone size breakpoint and MIC corresponding to that zone size breakpoint

Animal Health and Veterinary Laboratories Agency (AHVLA) historical veterinary breakpoint (under ongoing review)

Notes:

 Where zone size disc diffusion data collected using the BSAC method and MIC data are both available then it is possible to draw regression lines and investigate the MIC which approximately corresponds to the historical veterinary breakpoint of 13mm. This has been done for several compounds (highlighted in blue in the table above).  BSAC state that all Salmonella isolates should be reported as resistant to gentamicin and amikacin; resistance traits are used for epidemiological purposes (correlation with particular resistance mechanisms) in this report.  The 16 antibiotics with antibiotic code e.g. amikacin (AK) are the set used for Salmonella susceptibility testing.  Some Haemophilus-Pasteurella-Actinobacillus i.e. “HPA” organisms, for example Actinobacillus pleuropneumoniae, show a degree of intrinsic resistance to aminoglycosides.

* Erythromycin R < 21mm for beta-haemolytic streptococci; R < 19mm for other streptococci. ** Penicillin R < 19mm for beta-haemolytic streptococci; R < 16mm for other streptococci. *** Tetracycline R < 19mm for beta-haemolytic streptococci; R < 23mm for other streptococci.

Annexes

In Northern Ireland, an accredited CLSI method is used for testing and interpreting zones of inhibition (see table below). However, in Northern Ireland, Salmonella spp. isolates are also tested for Furazolidone, Framycetin, Apramycin and Spectinomycin using in-house break points.

Table A8.1: Antibiotic disc concentrations used in Northern Ireland

Expected Zone diameter (mm) Antibiotic Disc Resistant Intermediate Susceptible Ampicillin AMP10 <=13 14-16 >=17 Chloramphenicol C30 <=12 13-17 >=18 Gentamicin CN10 <=12 13-14 >=15 Kanamycin K30 <=13 14-17 >=18 Streptomycin S10 <=11 12-14 >=15 Sulphonamides S3.300 <=12 13-16 >=17 Tetracycline TE30 <=11 12-14 >=15 Trimethoprim W5 <=10 11-15 >=16 Furazolidone* FR100 Not available >=17 Nalidixic acid NA30 <=13 14-18 >=19 Ciprofloxacin CIP5 <=15 16-20 >=21 Cefotaxime CTX30 <=22 23-25 >=26 Ceftazidime CAZ30 <=17 18-20 >=21 Amoxicillin AMC30 <=13 14-17 >=18 Framycetin* FY100 Not available Apramycin* APR15 Not available Spectinomycin* SH100 Not available

Annexes

Annex 9: Comparison of 2015 ESBL results with those of previous UK surveys

A survey of multiple pathogens in pigs was performed by APHA in 2013. One component of the investigation examined ESBL producing E. coli in healthy UK pigs at slaughter. The method used in this survey differed to the method used in the 2015 EU monitoring. To enable comparison between this 2013 survey and the EU harmonised monitoring carried out in 2015, AHDB pork funded additional plating of pig caecal samples collected in 2015 on ESBL Brilliance agar (Oxoid, UK), as was done in the 2013 survey. The results of this survey have previously been published in the Journal of Antimicrobial Chemotherapy (Randall et al, 2014).

For the 2013 survey, samples from 637 pigs originating from 444 different farms, collected at 14 high-throughput abattoirs (which together process ~80% of slaughtered pigs in the UK) were collected between January and May and analysed.

For the 2015 survey, samples from 300 pigs from 300 different farms collected at six high throughput abattoirs (which together process ~60% of slaughtered pigs in GB) were collected between January and December and analysed.

Whilst the sample size, time of year for sampling and location of pigs varied between the two studies, both studies randomly sampled a large number of pigs from populations representative of ~60% or more of pigs slaughtered in the UK (in 2013) or GB (in 2015).

Table A9.1: Recovery of ESBL producing E. coli from pig caeca in 2015, compared with results from a 2013 pig survey

Number (and %) of caecal samples Number (and %) of caecal samples yielding E. coli on ESBL Brilliance agar yielding E. coli on ESBL Brilliance in 2013 agar in 2015

(132/637) 20.7% (63/300) 21.0%

Annexes

Annex 10: EU Harmonised Monitoring, results of Susceptibility testing in Salmonella

Table A10.1: Resistance in nine Salmonella spp. from pig caecal samples in 2015

No. (%) of isolates resistant based on Antibiotic CBPs ECVs Ampicillin 3 (33.3) 3 (33.3) Azithromycin * * Cefotaxime 0 0 Ceftazidime 0 0 Chloramphenicol 1 (11.1) 1 (11.1) Ciprofloxacin 0 1 (11.1) Colistin 0 0 Gentamicin 1 (11.1) 1 (11.1) Meropenem 0 0 Nalidixic acid 1 (11.1) 1 (11.1) Sulphonamide * 4 (44.4) Tetracyclines 3 (33.3) 3 (33.3) Tigecycline 0 0 Trimethoprim 1 (11.1) 1 (11.1)

Salmonella spp. from pigs (n=9)

* = No EUCAST breakpoint available

Annexes

Annex 11: Clinical surveillance data for isolates from bovine mastitis cases

Table A11.1: Resistance (interpreted using BSAC CBPs) in Escherichia coli mastitis isolates, 2013-2015

No. (%) of isolates resistant 2013 2014 2015 Antibiotic (n=159) (n=149) (n=88) Amoxi/Clav 13 (8.2) 11 (7.4) 13 (14.8) Ampicillin 43 (27) 36 (24.2) 23 (26.1) Cefotaxime - - - Cefpodoxime 1 (0.6) 3 (2) 2 (2.3) Ceftazidime - - - Cefalexin - - - Enrofloxacin 0 4 (2.7) 0 Neomycin 11 (6.9) 6 (4) 4 (4.5) Streptomycin 10 (6.3) 14 (9.4) 11 (12.5) Tetracycline 13 (8.2) 17 (11.4) 16 (18.2) Trimetho/Sulpho 13 (8.2) 13 (8.7) 9 (10.2)

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Table A11.2: Resistance (interpreted using BSAC CBPs) of staphylococci and streptococci from mastitis cases, 2013-2015

No. resistant / No. tested (Percentage resistant) S. aureus S. uberis S. dysgalactiae Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amoxi/Clav 26/106 (24.5) 12/82 (14.6) 9/77 (11.7) 0 0 0 0 0 0 Ampicillin 31/106 (29.2) 29/82 (35.4) 25/77 (32.5) 1/120 (0.8) 0 0 000 Penicillin 23/89 (25.8) 29/82 (35.4) 25/77 (32.5) 1/119 (0.8) 0 0 0 00 Neomycin 0 0 2/77 (2.6) 83/119 (69.7) 72/121 (59.5) 79/119 (66.4) 4/47 (8.5) 10/41 (24.4) 3/36 (8.3) Novobiocin 0 1/82 (1.2) 0 8/119 (6.7) 11/121 (9.1) 10/119 (8.4) 4/47 (8.5) 2/41 (4.9) 1/36 (2.8) Tetracycline 13/106 (12.3) 3/82 (3.7) 4/77 (5.2) 70/120 (58.3) 66/122 (54.1) 62/123 (50.4) 43/47 (91.5) 35/41 (85.4) 34/36 (94.4) Tylosin 1/106 (0.9) 1/82 (1.2) 2/77 (2.6) 24/120 (20) 20/122 (16.4) 14/123 (11.4) 4/47 (8.5) 4/41 (9.8) 2/36 (5.6)

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Annex 12: Clinical surveillance data for isolates from respiratory infections of cattle, sheep, and pigs

Table A12.1: Resistance (interpreted using BSAC CBPs) of Pasteurella multocida and Mannheimia haemolytica from respiratory infections of cattle, 2013-2015

No. (%) of isolates resistant P. multocida M. haemolytica 2013 2014 2015 2013 2014 2015 Antibiotic (n=39) (n=29) (n=42) (n=17) (n=12) (n=28) Amoxicillin/Clavulanic acid 0 0 0 0 0 0 Ampicillin 3 (7.7%) 1 (3.4%) 0 0 0 1 (3.6%) Cefalexin 0-- --- Cefpodoxime 1 (2.6%) 0 0 0 0 0 Enrofloxacin 000 000 Florfenicol 0 0 1 (2.5%) 0 2 (16.7%) 0 Tetracycline 19 (48.7%) 9 (31%) 16 (38.1%) 1 (5.9%) 3 (25%) 0 Trimethoprim/Sulphonamide 0 0 1 (2.4%) 0 0 0 Tylosin ------

Note: 33, 26 and 40 P. multocida isolates were tested for florfenicol susceptibility in 2013, 2014 and 2015, respectively. Only one P. multocida isolate was tested for cefalexin susceptibility in 2013.

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Table A12.2: Resistance (interpreted using BSAC CBPs) of Histophilus somni and Trueperella pyogenes from respiratory infections of cattle, 2013-2015

No. (%) of isolates resistant H. somni T. pyogenes 2013 2014 2015 2013 2014 2015 Antibiotic (n=14) (n=10) (n=7) (n=12) (n=13) (n=8) Amoxicillin/Clavulanic acid 0 0 0 0 0 0 Ampicillin 0 0 0 0 0 0 Cefalexin - - - 0 0 0 Cefpodoxime 0 0 0 - - - Enrofloxacin 0 0 0 - - - Florfenicol 0 0 0 0 0 0 Tetracycline 0 0 0 7 (58.3%) 8 (61.5%) 5 (62.5%) Trimethoprim/Sulphonamide 0 0 0 6 (50%) 3 (23.1%) 3 (37.5%) Tylosin - - - 0 0 1 (12.5%)

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Annex 13: Clinical surveillance data for isolates from respiratory infections of pigs

Table A13.1: Resistance (interpreted using BSAC CBPs) of Pasteurella multocida and Actinobacillus pleuropneumoniae from respiratory infections of pigs, 2013-2015

No. resistant / No. tested (Percentage resistant) Pigs, P. multocida Pigs, A. pleuropneumoniae Antibiotic 2013 2014 2015 2013 2014 2015 Amoxicillin/Clavulanic acid 0 0 0 0 0 0 Ampicillin 3/39 (7.7) 1/33 (3) 0 3/17 (17.6) 0 2/22 (9.1) Apramycin 4/39 (10.3) 1/32 (3.1) 0 8/17 (47.1) 4/14 (28.6) 2/22 (9.1) Cefpodoxime 0 0 0 0 0 0 Doxycycline 1/24 (4.2) 0 0 1/15 (6.7) 0 0 Enrofloxacin 0 0 0 0 0 0 Florfenicol 0 0 0 0 0 0 Lincomycin ------Neomycin 4/39 (10.3) 0 1/12 (8.3) 7/17 (41.2) 5/14 (35.7) 2/22 (9.1) Spectinomycin 1/39 (2.6) 0 0 6/17 (35.3) 4/14 (28.6) 2/22 (9.1) Streptomycin 3/24 (12.5) 3/27 (11.1) 2/11 (18.2) 5/15 (33.3) 5/14 (35.7) 2/22 (9.1) Tetracycline 33/39 (84.6) 27/33 (81.8) 8/12 (66.7) 6/17 (35.3) 4/14 (28.6) 8/22 (36.4) Trimethoprim/Sulphonamide 9/39 (23.1) 11/33 (33.3) 1/12 (8.3) 5/17 (29.4) 0 9/22 (40.9) Tylosin 4/24 (16.7) 1/28 (3.6) 3/11 (27.3) 8/15 (53.3) 13/14 (92.9) 20/22 (90.9)

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Annex 14: Clinical surveillance data for isolates from respiratory infections of sheep

Table A14.1: Resistance (interpreted using BSAC CBPs) of Pasteurella multocida and Mannheimia haemolytica from sheep, 2013-2015

No. resistant / No. tested (Percentage resistant) Sheep, P. multocida Sheep, M. haemolytica Antibiotic 2013 2014 2015 2013 2014 2015 Amoxicillin/Clavulanic acid 0 0 0 0 0 0 Ampicillin 0 0 1/3 (33.3) 0 0 0 Cefalexin ------Cefpodoxime 0 0 0 0 0 0 Enrofloxacin 000 000 Florfenicol 0 0 0 0 0 0 Tetracycline 1/5 (20) 0 0 0 2/24 (8.3) 1/35 (2.9) Trimethoprim/Sulphonamide 0 0 0 0 1/24 (4.2) 1/35 (2.9) Tylosin ------

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Table A14.2: Resistance (interpreted using BSAC CBPs) of Bibersternia trehalosi and Trueperella pyogenes from sheep, 2013-2015

No. resistant / No. tested (Percentage resistant) Sheep, B. trehalosi Sheep, T. pyogenes Antibiotic 2013 2014 2015 2013 2014 2015 Amoxicillin/Clavulanic acid 0 0 0 0 0 0 Ampicillin 0 0 0 0 0 0 Cefalexin ---000 Cefpodoxime 0 0 0 - - - Enrofloxacin 000 - - - Florfenicol 000000 Tetracycline 1/18 (5.6) 0 1/40 (2.5) 2/5 (40) 2/10 (20) 0 Trimethoprim/Sulphonamide 0 0 1/40 (2.5) 0 4/9 (44.4) 0 Tylosin ---000

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Annex 15: ‘Other Veterinary Pathogens’

Table A15.1: MIC values of Brachyspira hyodysenteriae isolates from infections of pigs to tiamulin, 2010-2015

MIC Year <0.06 0.12 0.25 0.5 1 2 4 8 >8 2010 10 1 - 1 1 - - - - 2011 10 - - - - 2 - - - 2012 2 - 2 - - 2 1 - 2 2013 - - 1 2 1 - 1 - 3 2014 - - - - - 2 - 1 1 2015 - - 3 - - 1 - 1 -

Annexes

Table A15.2: Resistance (interpreted using BSAC CBPs) of Streptococcus suis from infections of pigs, 2013-2015

No. (%) of isolates resistant Pigs, S. suis 2013 2014 2015 Antibiotic (n=55) (n=64) (n=63) Ampicillin 0 0 0 Penicillin 1 (1.8%) 0 0 Cefalexin --- Enrofloxacin 000 Lincomycin 25 (45.5%) 21 (32.8%) 26 (41.3%) Tetracycline 52 (94.5%) 61 (95.3%) 59 (93.7%) Trimethoprim/Sulphonamide 7 (12.7%) 15 (23.4%) 14 (22.2%) Tylosin 26 (47.3%) 24 (37.5%) 37 (58.7%)

Table A15.3: Resistance (interpreted using BSAC CBPs) of Staphylococcus aureus from infections of chickens, 2013-2015

No. (%) of isolates resistant Chickens, S. aureus 2013 2014 2015 Antibiotic (n=26) (n=26) (n=8) Amoxicillin/Clavulanic acid 0 0 0 Ampicillin 0 0 0 Doxycycline 3 (11.5%) 2 (7.7%) 0 Enrofloxacin 1 (3.8%) 0 0 Erythromycin 2 (8%) 2 (8%) 1 (12.5%) Lincomycin 2 (7.7%) 2 (7.7%) 1 (12.5%) Tetracycline 3 (11.5%) 3 (11.5%) 1 (12.5%) Trimethoprim/Sulphonamide 0 0 0 Tylosin 1 (3.8%) 0 0

Note: Only 25 S. aureus were tested for susceptibility to amoxicillin/clavulanic acid and erythromycin in 2013 and 2014

Annexes

Table A15.4: Resistance (interpreted using BSAC CBPs) of Erysipelothrix rhusiopathiae from infections of pigs, 2013-2015

No. (%) of isolates resistant Pigs, E. rhusiopathiae 2013 2014 2015 Antibiotic (n=11) (n=11) (n=6) Amoxicillin/Clavulanic acid - - - Ampicillin 0 0 0 Enrofloxacin 0 1 (9.1%) 0 Lincomycin 0 0 0 Tetracycline 4 (36.4%) 3 (27.3%) 2 (33.3%) Trimethoprim/Sulphonamide 8 (72.7%) 2 (18.2%) 2 (33.3%) Tylosin 0 0 0

Table A15.5: Resistance (interpreted using BSAC CBPs) of Listeria monocytogenes from infections of sheep, 2013-2015

No. (%) of isolates resistant Sheep, Listeria monocytogenes 2013 2014 2015 Antibiotic (n=10) (n=2) (n=4) Amoxicillin/Clavulanic acid 0 0 0 Ampicillin 0 0 0 Cefalexin 3 (30%) 0 3 (75%) Florfenicol 0 0 0 Tetracycline 0 1 (50%) 0 Trimethoprim/Sulphonamide 0 0 0 Tylosin 0 0 0

Annexes

Table A15.6: Resistance (interpreted using BSAC CBPs) of Streptococcus dysgalactiae from infections of sheep, 2013-2015

No. (%) of isolates resistant Sheep, Streptococcus dysgalactiae 2013 2014 2015 Antibiotic (n=26) (n=14) (n=18) Amoxicillin/Clavulanic acid 0 0 0 Ampicillin 0 0 0 Cefalexin 0 0 0 Florfenicol 0 0 0 Tetracycline 22 (84.6%) 14 (100%) 18 (100%) Trimethoprim/Sulphonamide 0 0 0 Tylosin 1 (3.8%) 3 (21.4%) 0

Note: Only 11, 7, and 4 S. dysgalactiae were tested for susceptibility to florfenicol and trimethoprim/sulphonamide in 2013, 2014, and 2015, respectively

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Annex 16: Clinical surveillance data for E. coli

Table A16.1 – Resistance in all E. coli from cattle, sheep, pigs, chickens and turkeys (combined) in England & Wales, Northern Ireland and Scotland

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amikacin 4/856 (0.5) 2/590 (0.3) 3/524 (0.6) ------Amoxi/Clav 447/1296 (34.5) 314/1045 (30) 282/1034 (27.3) 756/1304 (58) 496/986 (50.3) 471/931 (50.6) 95/336 (28.3) 72/293 (24.6) 69/346 (19.9) Ampicillin 892/1400 (63.7) 733/1144 (64.1) 713/1101 (64.8) 992/1304 (76.1) 798/986 (80.9) 748/931 (80.3) 158/336 (47) 136/293 (46.4) 130/346 (37.6) Apramycin 85/1360 (6.3) 73/1118 (6.5) 60/1073 (5.6) 212/1304 (16.3) 116/980 (11.8) 138/917 (15) 7/248 (2.8) 3/236 (1.3) 3/271 (1.1) Cefotaxime 98/857 (11.4) 80/593 (13.5) 49/526 (9.3) - - - 0 0 0 Cefpodoxime 27/434 (6.2) 19/481 (4) 34/474 (7.2) 819/1304 (62.8) 396/980 (40.4) 403/912 (44.2) 15/247 (6.1) 12/236 (5.1) 8/271 (3) Ceftazidime 53/857 (6.2) 44/593 (7.4) 34/526 (6.5) - - - 0 0 - Chloramphenicol 440/856 (51.4) 298/590 (50.5) 244/524 (46.6) - - - 0 0/2 (0) 0/1 (0) Doxycycline 86/371 (23.2) 157/452 (34.7) 132/451 (29.3) - - - 0 - - Enrofloxacin 114/1400 (8.1) 93/1144 (8.1) 118/1101 (10.7) 647/1304 (49.6) 418/986 (42.4) 414/931 (44.5) 24/337 (7.1) 13/293 (4.4) 12/346 (3.5) Florfenicol 295/969 (30.4) 209/764 (27.4) 174/709 (24.5) 669/1304 (51.3) 448/919 (48.7) 413/878 (47) 36/240 (15) 33/223 (14.8) 28/257 (10.9) Neomycin 398/1282 (31) 287/1049 (27.4) 266/1030 (25.8) 1304/1304 (100) 986/986 (100) 932/932 (100) 44/331 (13.3) 26/293 (8.9) 26/346 (7.5) Spectinomycin 565/1360 (41.5) 441/1118 (39.4) 462/1073 (43.1) - - - 72/248 (29) 56/236 (23.7) 60/271 (22.1) Streptomycin 556/933 (59.6) 442/742 (59.6) 443/685 (64.7) - - - 8/89 (9) 7/55 (12.7) 2/73 (2.7) Tetracycline 932/1400 (66.6) 779/1144 (68.1) 708/1101 (64.3) 1071/1304 (82.1) 770/986 (78.1) 745/927 (80.4) 175/337 (51.9) 169/293 (57.7) 160/346 (46.2) Trimetho/Sulpho 508/1400 (36.3) 442/1144 (38.6) 420/1101 (38.1) 874/1304 (67) 629/986 (63.8) 615/926 (66.4) 85/335 (25.4) 76/293 (25.9) 64/346 (18.5)

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Table A16.2 – Resistance in all E. coli from cattle (all ages) in England & Wales, Northern Ireland and Scotland

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amikacin 4/706 (0.6) 2/492 (0.4) 2/441 (0.5) ------Amoxi/Clav 385/780 (49.4) 271/533 (50.8) 223/494 (45.1) 683/1060 (64) 424/733 (58) 443/714 (62) 75/183 (41) 61/146 (41.8) 44/150 (29.3) Ampicillin 617/780 (79.1) 431/533 (80.9) 392/494 (79.4) 936/1057 (89) 630/732 (86) 602/714 (84) 91/184 (49.5) 76/146 (52.1) 58/150 (38.7) Apramycin 50/761 (6.6) 22/517 (4.3) 22/480 (4.6) 186/1060 (18) 83/729 (11) 105/709 (15) 2/96 (2.1) 2/90 (2.2) 2/77 (2.6) Cefotaxime 94/707 (13.3) 77/495 (15.6) 46/443 (10.4) ------Cefpodoxime - - - 703/1059 (66) 308/731 (42) 328/704 (47) 9/96 (9.4) 12/90 (13.3) 0/78 (0) Ceftazidime 52/707 (7.4) 42/495 (8.5) 32/443 (7.2) ------Chloramphenicol 386/706 (54.7) 271/492 (55.1) 228/441 (51.7) - - - - 0/1 (0) - Doxycycline ------Enrofloxacin 93/780 (11.9) 60/533 (11.3) 58/494 (11.7) 583/1059 (55) 368/732 (50) 361/714 (51) 20/184 (10.9) 11/146 (7.5) 6/150 (4) Florfenicol 262/724 (36.2) 190/507 (37.5) 147/455 (32.3) 615/1059 (58) 416/728 (57) 402/712 (56) 33/95 (34.7) 32/90 (35.6) 22/77 (28.6) Neomycin 332/761 (43.6) 250/517 (48.4) 217/480 (45.2) 1058/1058 (100) 732/732 (100) 714/714 (100) 38/179 (21.2) 21/146 (14.4) 20/150 (13.3) Spectinomycin 380/761 (49.9) 231/517 (44.7) 218/480 (45.4) - - - 44/96 (45.8) 34/90 (37.8) 29/77 (37.7) Streptomycin 439/706 (62.2) 316/492 (64.2) 315/441 (71.4) - - - 7/88 (8) 7/55 (12.7) 1/72 (2.4) Tetracycline 595/780 (76.3) 424/533 (79.5) 369/494 (74.7) 910/1060 (86) 597/732 (82) 593/711 (83) 106/184 (57.6) 81/146 (55.5) 65/150 (43.3) Trimetho/Sulph 359/780 (46) 261/533 (49) 224/494 (45.3) 758/1060 (72) 503/732 (69) 505/711 (71) 45/182 (24.7) 43/146 (29.5) 26/150 (17.3)

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Table A16.3 – Resistance in all E. coli from pigs (all ages) in England & Wales, Northern Ireland and Scotland

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amikacin ------Amoxi/Clav 3/76 (3.9) 6/151 (4) 8/159 (5) 26/85 (31) 33/101 (33) 21/93 (23) 1/8 (12.5) 3/11 (27.3) 5/22 (22.7) Ampicillin 51/101 (50.5) 104/180 (57.8) 102/182 (56) 65/84 (77) 71/101 (70) 67/93 (72) 2/8 (25) 6/11 (54.5) 6/22 (27.3) Apramycin 14/101 (13.9) 34/180 (18.9) 31/182 (17) 11/85 (13) 20/100 (20) 20/93 (22) 1/8 (12.5) 0/11 (0) 0/22 (0) Cefotaxime ------Cefpodoxime 4/101 (4) 7/180 (3.9) 3/182 (1.6) 42/85 (49) 28/100 (28) 26/93 (28) 0/8 (0) 0/11 (0) 0/21 (0) Ceftazidime ------Chloramphenicol ------Doxycycline 45/76 (59.2) 90/151 (59.6) 79/159 (49.7) ------Enrofloxacin 8/101 (7.9) 17/180 (9.4) 7/182 (3.8) 34/85 (40) 23/101 (23) 28/93 (30) 1/8 (12.5) 0/11 (0) 2/22 (9.1) Florfenicol 5/76 (6.6) 8/151 (5.3) 16/159 (10.1) 24/85 (28) 12/100 (12) 12/93 (13) 1/8 (12.5) 0/11 (0) 1/22 (4.5) Neomycin 10/101 (9.9) 7/180 (3.9) 15/182 (8.2) 85/85 (100) 101/101 (100) 93/93 (100) 1/8 (12.5) 0/11 (0) 0/22 (0) Spectinomycin 34/101 (33.7) 86/180 (47.8) 78/182 (42.9) - - - 2/8 (25) 5/11 (45.4) 3/22 (13.6) Streptomycin 33/76 (43.4) 82/151 (54.3) 71/159 (44.7) - - - 0 0 0 Tetracycline 75/101 (74.3) 142/180 (78.9) 121/182 (66.5) 66/85 (78) 81/101 (80) 76/93 (82) 5/8 (62.5) 8/11 (72.7) 9/22 (40.9) Trimetho/Sulph 51/101 (50.5) 102/180 (56.7) 99/182 (54.4) 68/85 (80) 79/101 (78) 70/92 (76) 3/8 (37.5) 6/11 (54.5) 3/22 (13.6)

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Table A16.4 – Resistance in all E. coli from sheep (all ages) in England & Wales, Northern Ireland and Scotland

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amikacin 0/150 (0) 0/98 (0) 1/83 (1.2) ------Amoxi/Clav 48/224 (21.4) 26/130 (20) 21/133 (15.8) 31/98 (32) 23/83 (28) 24/66 (36) 10/45 (22.2) 8/29 (27.6) 11/48 (22.9) Ampicillin 125/224 (55.8) 71/130 (54.6) 74/133 (55.6) 72/98 (73) 60/83 (72) 44/66 (67) 18/44 (40.9) 11/29 (37.9) 19/48 (39.6) Apramycin 3/204 (1.5) 3/120 (2.5) 1/119 (0.8) 8/98 (8) 8/83 (10) 7/66 (11) 0/44 (0) 0/28 (0) 1/46 (2.2) Cefotaxime 4/150 (2.7) 3/98 (3.1) 3/83 (3.6) ------Cefpodoxime - - - 43/98 (44) 30/83 (36) 25/66 (38) 0/43 (0) 0/28 (0) 0/46 (0) Ceftazidime 1/150 (0.7) 2/98 (2) 2/83 (2.4) ------Chloramphenicol 54/150 (36) 27/98 (27.6) 16/83 (19.3) - - - - 0/1 (0) 0/1 (0) Doxycycline ------Enrofloxacin 8/224 (3.6) 1/130 (0.8) 2/133 (1.5) 18/98 (18) 18/83 (22) 11/66 (17) 0/45 (0) 0/29 (0) 2/48 (3.6) Florfenicol 28/169 (16.6) 11/106 (10.4) 11/95 (11.6) 27/97 (28) 19/83 (23) 19/66 (29) 1/44 (2.3) 1/28 (3.6) 5/44 (11.4) Neomycin 36/205 (17.6) 9/121 (7.4) 21/121 (17.4) 98/98 (100) 83/83 (100) 66/66 (100) 3/44 (6.8) 4/29 (13.8) 4/48 (8.3) Spectinomycin 108/204 (52.9) 52/120 (43.3) 67/119 (56.3) - - - 13/44 (29.5) 7/28 (25) 13/46 (28.3) Streptomycin 84/151 (55.6) 44/99 (44.4) 57/85 (67.1) - - - 1/1 (100) 0 1/1 (100) Tetracycline 153/224 (68.3) 89/130 (68.5) 86/133 (64.7) 70/97 (72) 60/83 (72) 48/66 (72) 24/45 (53.3) 18/29 (62.1) 26/48 (54.2) Trimetho/Sulph 62/224 (27.7) 28/130 (21.5) 36/133 (27.1) 40/98 (41) 32/83 (39) 22/66 (33) 7/45 (15.6) 7/29 (24.1) 7/48 (14.6)

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Table A16.5 – Resistance in all E. coli from chickens (all ages) in England & Wales, Northern Ireland and Scotland

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amikacin ------Amoxi/Clav 11/215 (5.1) 11/230 (4.8) 30/248 (12.1) 8/22 (36) 3/33 (9) 5/25 (20) 8/93 (8.6) 0/94 (0) 9/114 (7.9) Ampicillin 94/289 (32.5) 124/294 (42.2) 143/287 (49.8) 12/22 (55) 16/33 (48) 18/26 (72) 44/93 (47.3) 32/94 (34) 38/114 (33.3) Apramycin 18/288 (6.3) 14/294 (4.8) 6/287 (2.1) 5/22 (23) 1/33 (3) 2/26 (8) 4/93 (4.3) 1/94 (1.1) 0/114 (0) Cefotaxime ------Cefpodoxime 23/288 (8) 12/294 (4.1) 31/287 (10.8) 18/22 (82) 14/33 (42) 14/26 (54) 6/93 (6.5) 0/94 (0) 8/114 (7) Ceftazidime ------Chloramphenicol ------Doxycycline 40/289 (13.8) 65/294 (22.1) 49/287 (17.1) ------Enrofloxacin 5/289 (1.7) 14/294 (4.8) 50/287 (17.4) 5/22 (23) 3/33 (9) 6/26 (23) 3/93 (3.2) 1/94 (1.1) 1/114 (0.9) Florfenicol ------1/93 (1.1) 0/94 (0) 0/114 (0) Neomycin 20/214 (9.3) 21/230 (9.1) 13/247 (5.3) 22/22 (100) 33/33 (100) 26/26 (100) 2/93 (2.2) 1/94 (1.1) 2/114 (1.8) Spectinomycin 43/288 (14.9) 71/294 (24.1) 99/287 (34.5) - - - 13/93 (14) 9/94 (9.6) 14/114 (12.3) Streptomycin ------Tetracycline 104/289 (36) 120/294 (40.8) 128/287 (44.6) 9/22 (41) 12/33 (36) 13/26 (50) 37/93 (39.8) 52/94 (55.3) 52/114 (45.6) Trimetho/Sulph 36/289 (12.5) 50/294 (17) 60/287 (20.9) 5/22 (23) 5/33 (15) 7/26 (27) 30/93 (32.3) 18/94 (19.1) 20/114 (17.5)

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Table A16.6 – Resistance in all E. coli from turkeys (all ages) in England & Wales, Northern Ireland and Scotland

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Amikacin ------Amoxi/Clav 0/1 (0) 0/1 (0) - 0 2/7 (29) 1/3 (33) 1/7 (14.3) 0/13 (0) 0/12 (0) Ampicillin 5/6 (83.3) 3/7 (42.9) 2/5 (40) 0 5/7 (71) 2/3 (66) 3/7 (42.9) 11/13 (84.6) 9/12 (75) Apramycin 0/6 (0) 0/7 (0) 0/5 (0) 0 0/7 (0) 1/3 (33) 0/7 (0) 0/13 (0) 0/12 (0) Cefotaxime ------Cefpodoxime 0/6 (0) 0/7 (0) 0/5 (0) 0 2/7 (29) 2/3 (66) 0/7 (0) 0/13 (0) 0/12 (0) Ceftazidime ------Chloramphenicol ------Doxycycline 1/6 (16.7) 2/7 (28.6) 4/5 (80) ------Enrofloxacin 0/6 (0) 1/7 (14.3) 1/5 (20) 0 1/7 (0.1) - 0/7 (0) 1/13 (7.7) 1/12 (8.3) Florfenicol ------0 0 0 Neomycin 0/1 (0) 0/1 (0) - 0 7/7 (100) 3/3 (100) 0/7 (0) 0/13 (0) 0/12 (0) Spectinomycin 0/6 (0) 1/7 (14.3) 0/5 (0) - - - 0/7 (0) 1/13 (7.7) 1/12 (8.3) Streptomycin ------Tetracycline 5/6 (83.3) 4/7 (57.1) 4/5 (80) 0 6/7 (86) 2/3 (66) 3/7 (42.9) 10/13 (76.9) 8/12 (66.7) Trimetho/Sulph 0/6 (0) 1/7 (14.3) 1/5 (20) 0 2/7 (29) 2/3 (66) 0/7 (0) 2/13 (7.7) 8/12 (66.7)

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Table A16.7 – Resistance in E. coli from cattle in England & Wales, Northern Ireland and Scotland in 2013

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Pre-weaning Adult Neonatal Pre-weaning Adult Neonatal Pre-weaning Adult Amikacin 3/599 (0.5) 0/61 (0) 0/3 (0) - - - 0 0 0

Amoxi/Clav 330/629 (52.5) 36/86 (41.9) 2/16 (12.5) 334/497 (67) - - 42/129 (32.6) 30/39 (76.9) 3/14 (21.4) Ampicillin 511/629 (81.2) 69/86 (80.2) 5/16 (31.3) 452/497 (91) - - 54/130 (41.5) 33/39 (84.6) 4/14 (28.5) Apramycin 39/621 (6.3) 5/78 (6.4) 1/14 (7.1) 98/497 (20) - - 0/54 (0) 1/39 (2.6) 1/2 (50) Cefotaxime 75/599 (12.5) 12/61 (19.7) 0/4 (0) - - - 0 0 0 Ceftazidime 46/599 (7.7) 4/61 (6.6) 0/4 (0) - - - 0 0 0 Chloramphenicol 333/599 (55.6) 34/61 (55.7) 2/3 (66.7) - - - 0 0 0 Enrofloxacin 75/629 (11.9) 9/86 (10.5) 2/16 (12.5) 245/497 (49) - - 11/130 (8.5) 7/39 (17.9) 2/14 (14.3) Florfenicol 215/606 (35.5) 33/69 (47.8) 1/5 (20) 241/497 (48) - - 15/54 (27.8) 18/39 (46.2) 0/1 (0) Neomycin 276/621 (44.4) 38/78 (48.7) 1/14 (7.1) 496/496 (100) - - 22/125 (17.6) 14/39 (35.9) 2/14 (14.3) Spectinomycin 329/621 (53) 28/78 (35.9) 4/14 (28.6) - - - 24/54 (44.4) 20/39 (51.3) 0/2 (0) Streptomycin 372/599 (62.1) 43/61 (70.5) 2/3 (66.7) - - - 3/76 (3.9) 0 4/12 (33.3) Tetracycline 489/629 (77.7) 67/86 (77.9) 7/16 (43.8) 226/497 (45) - - 64/130 (49.2) 35/39 (89.7) 6/14 (42.9) Trim/Sulpho 290/629 (46.1) 46/86 (53.5) 4/16 (25) 224/497 (45) - - 25/130 (19.2) 17/37 (45.9) 3/14 (21.4)

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Table A16.8 – Resistance in E. coli from cattle in England & Wales, Northern Ireland and Scotland in 2014

Amoxi/Clav 231/449 (51.4) 20/44 (45.5) 2/8 (25) 207/321 (64) - - 35/103 (34) 25/37 (67.6) 1/5 (20) Ampicillin 365/449 (81.3) 32/44 (72.7) 6/8 (75) 287/321 (89) - - 46/103 (44.7) 28/37 (75.7) 2/5 (40) Apramycin 20/442 (4.5) 2/37 (5.4) 0/7 (0) 43/320 (13) - - 1/52 (1.9) 1/37 (2.7) 0 Cefotaxime 64/432 (14.8) 7/28 (25) 4/6 (66.7) - - - 0 0 0 Ceftazidime 32/432 (7.4) 5/28 (17.9) 3/6 (50) - - - 0 0 0 Chloramphenicol 237/432 (54.9) 12/28 (42.9) 3/3 (100) - - - 1/1 (100) 0 0 Enrofloxacin 52/449 (11.6) 4/44 (9.1) 2/8 (25) 163/321 (51) - - 5/103 (4.9) 6/37 (16.2) 0/5 (0) Florfenicol 163/439 (37.1) 10/35 (28.6) 2/3 (66.7) 187/320 (58) - - 14/52 (26.9) 18/37 (48.6) 0 Neomycin 218/442 (49.3) 18/37 (48.6) 1/7 (14.3) 321/321 (100) - - 11/103 (10.7) 10/37 (27) 0/5 (0) Spectinomycin 204/442 (46.2) 11/37 (29.7) 1/7 (14.3) - - - 18/52 (34.6) 16/37 (43.2) 0 Streptomycin 278/432 (64.4) 14/28 (50) 2/3 (66.7) - - - 7/50 (14) 0 0/5 (0) Tetracycline 357/449 (79.5) 37/44 (84.1) 5/8 (62.5) 260/321 (81) - - 45/103 (43.7) 33/37 (89.2) 2/5 (40) Trim/Sulpho 217/449 (48.3) 22/44 (50) 3/8 (37.5) 223/321 (69) - - 23/103 (22.3) 19/37 (51.4) 1/5 (20)

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Table A16.9 – Resistance in E. coli from cattle in England & Wales, Northern Ireland and Scotland in 2015

Amoxi/Clav 181/376 (48.1) 23/75 (30.7) 5/15 (33.3) 201/331 (61) - - 28/114 (24.6) 15/30 (50) 1/6 (16.7) Ampicillin 310/376 (82.4) 52/75 (69.3) 10/15 (66.7) 296/331 (89) - - 40/114 (35.1) 16/30 (1.9) 2/6 (33.3) Apramycin 12/369 (3.3) 8/73 (11) 1/13 (7.7) 34/329 (10) - - 2/45 (4.4) 0/30 (0) 0/2 (0) Cefotaxime 37/352 (10.5) 3/59 (5.1) 2/9 (22.2) - - - 0 0 0 Ceftazidime 28/352 (8) 2/59 (3.4) 1/9 (11.1) - - - 0 0 0 Chloramphenicol 174/352 (49.4) 35/59 (59.3) 3/7 (42.9) - - - 0 0 0 Enrofloxacin 38/376 (10.1) 11/75 (14.7) 4/15 (26.7) 167/331 (50) - - 2/114 (1.8) 4/30 (7.5) 0/6 (0) Florfenicol 105/359 (29.2) 25/61 (41) 3/9 (33.3) 187/331 (56) - - 10/45 (22.2) 12/30 (2.5) 0/2 (0) Neomycin 161/369 (43.6) 39/73 (53.4) 6/13 (46.2) 331/331 (100) - - 11/114 (9.6) 8/30 (3.75) 1/6 (16.7) Spectinomycin 173/369 (46.9) 29/73 (39.7) 4/13 (30.8) - - - 20/45 (44.4) 8/30 (3.75) 1/2 (50) Streptomycin 250/352 (71) 46/59 (78) 4/7 (57.1) - - - 1/68 (1.5) 0 0/4 (0) Tetracycline 284/376 (75.5) 55/75 (73.3) 11/15 (73.3) 284/331 (86) - - 46/114 (40.4) 18/30 (1.7) 1/6 (16.7) Trim/Sulpho 168/376 (44.7) 34/75 (45.3) 7/15 (46.7) 245/331 (74) - - 17/114 (14.9) 9/30 (3.3) 0/6 (0)

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Table A16.10 – Resistance in E. coli from pigs in England & Wales, Northern Ireland and Scotland in 2013

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Post-weaning Adult Neonatal Post-weaning Adult Neonatal Post-weaning Adult Amoxi/Clav 1/18 (5.6) 2/31 (6.5) 0/4 (0) 10/25 (40) - - 0/2 (0) 1/4 (25) 0/1 (0) Ampicillin 16/28 (57.1) 20/35 (57.1) 3/6 (50) 22/25 (88) - - 1/2 (50) 1/4 (25) 0/1 (0) Apramycin 0/28 (0) 9/35 (25.7) 1/6 (16.7) 4/25 (16) - - 0/2 (0) 1/4 (25) 0/1 (0) Cefpodoxime 1/28 (3.6) 1/35 (2.9) 0/6 (0) 17/25 (68) - - 0/2 (0) 0/4 (0) 0

Doxycycline 11/18 (61.1) 20/31 (64.5) 1/4 (25) - - - 0 0 0 Enrofloxacin 3/28 (10.7) 2/35 (5.7) 0/6 (0) 13/25 (52) - - 0/2 (0) 1/4 (25) 0/1 (0) Florfenicol 0/18 (0) 4/31 (12.9) 0/4 (0) 4/25 (16) - - 0/2 (0) 1/4 (25) 0/1 (0) Neomycin 2/28 (7.1) 5/35 (14.3) 1/6 (16.7) 25/25 (100) - - 0/2 (0) 1/4 (25) 0/1 (0) Spectinomycin 9/28 (32.1) 17/35 (48.6) 1/6 (16.7) - - - 0/2 (0) 1/4 (25) 0/1 (0) Streptomycin 9/18 (50) 16/31 (51.6) 0/4 (0) - - - 0 0 0 Tetracycline 18/28 (64.3) 26/35 (74.3) 4/6 (66.7) 22/25 (88) - - 2/2 (100) 3/4 (75) 0/1 (0) Trimetho/Sulph 14/28 (50) 21/35 (60) 2/6 (33.3) 21/25 (84) - - 1/2 (50) 1/4 (25) 0/1 (0)

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Table A16.11 – Resistance in E. coli from pigs in England & Wales, Northern Ireland and Scotland in 2014

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Post-weaning Adult Neonatal Post--weaning Adult Neonatal Post--weaning Adult Amoxi/Clav 0/25 (0) 3/78 (3.8) 0/6 (0) 11/43 (26) - - 2/7 (28.6) 0/1 (0) 0/1 (0) Ampicillin 19/39 (48.7) 51/84 (60.7) 3/7 (42.9) 28/43 (65) - - 3/7 (42.9) 0/1 (0) 1/1 (100) Apramycin 1/39 (2.6) 31/84 (36.9) 0/7 (0) 8/43 (19) - - 0/7 (0) 0/1 (0) 0/1 (0) Cefpodoxime 0/39 (0) 1/84 (1.2) 0/7 (0) 9/43 (21) - - 0/7 (0) 0/1 (0) 0

Doxycycline 12/25 (48) 51/78 (65.4) 3/6 (50) - - - 0 0 0 Enrofloxacin 7/39 (17.9) 5/84 (6) 1/7 (14.3) 10/43 (23) - - 0/7 (0) 0/1 (0) 0/1 (0) Florfenicol 1/25 (4) 4/78 (5.1) 0/6 (0) 9/43 (21) - - 0/7 (0) 0/1 (0) 0/1 (0) Neomycin 2/39 (5.1) 2/84 (2.4) 1/7 (14.3) 43/43 (100) - - 0/7 (0) 0/1 (0) 0/1 (0) Spectinomycin 20/39 (51.3) 44/84 (52.4) 3/7 (42.9) - - - 3/7 (42.9) 1/1 (100) 0/1 (0) Streptomycin 10/25 (40) 49/78 (62.8) 3/6 (50) - - - 0 0 0 Tetracycline 30/39 (76.9) 69/84 (82.1) 5/7 (71.4) 33/43 (77) - - 5/7 (71.4) 1/1 (100) 0/1 (0) Trimetho/Sulph 19/39 (48.7) 54/84 (64.3) 2/7 (28.6) 40/43 (93) - - 3/7 (42.9) 1/1 (100) 0/1 (0)

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Table A16.12 – Resistance in E. coli from pigs in England & Wales, Northern Ireland and Scotland in 2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Post-weaning Adult Neonatal Post--weaning Adult Neonatal Post--weaning Adult Amoxi/Clav 2/30 (6.7) 4/93 (4.3) 1/7 (14.3) 10/47 (21) - - 1/5 (20) 3/15 (20) 1/1 (100) Ampicillin 18/39 (46.2) 63/97 (64.9) 3/7 (42.9) 36/47 (77) - - 1/5 (20) 4/15 (26.7) 1/1 (100) Apramycin 0/39 (0) 25/97 (25.8) 0/7 (0) 10/47 (21) - - 0/5 (0) 0/15 (0) 1/1 (0) Cefpodoxime 0/39 (0) 2/97 (2.1) 0/7 (0) 9/47 (19) - - 0/5 (0) 0/15 (0) 0

Doxycycline 13/30 (43.3) 51/93 (54.8) 2/7 (28.6) - - - 0 0 0 Enrofloxacin 1/39 (2.6) 5/97 (5.2) 0/7 (0) 16/47 (34) - - 0/5 (0) 2/15 (13.3) 0/1 (0) Florfenicol 1/30 (3.3) 13/93 (14) 1/7 (14.3) 4/47 (9) - - 0/5 (0) 0/15 (0) 1/1 (100) Neomycin 1/39 (2.6) 12/97 (12.4) 0/7 (0) 47/47 (100) - - 0/5 (0) 0/15 (0) 0/1 (0) Spectinomycin 15/39 (38.5) 48/97 (49.5) 2/7 (28.6) - - - 0/5 (0) 0/15 (0) 0/1 (0) Streptomycin 10/30 (33.3) 45/93 (48.4) 4/7 (57.1) - - - 0 0 0 Tetracycline 28/39 (71.8) 67/97 (69.1) 3/7 (42.9) 40/47 (85) - - 3/5 (60) 5/15 (33.3) 1/1 (100) Trimetho/Sulph 17/39 (43.6) 63/97 (64.9) 3/7 (42.9) 37/47 (78) - - 0/5 (0) 3/15 (20) 0/1 (0)

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Table A16.13 – Resistance in E. coli from sheep in England & Wales, Northern Ireland and Scotland in 2013

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Pre-weaning Adult Neonatal Post-weaning Adult Neonatal Pre--weaning Adult Amoxi/Clav 44/173 (25.4) 2/15 (13.3) 0/18 (0) 1/6 (17) - - 5/28 (17.9) 4/12 (33.3) 1/3 (33.3) Ampicillin 108/173 (62.4) 4/15 (26.7) 6/18 (33.3) 6/18 (33.3) - - 10/27 (37) 5/12 (41.7) 3/3 (100) Apramycin 3/170 (1.8) 0/10 (0) 0/9 (0) 0/9 (0) - - 0/27 (0) 0/12 (0) 0/3 (0) Cefotaxime 4/139 (2.9) 0/3 (0) 0/1 (0) 0/1 (0) - - 0 0 0 Ceftazidime 1/139 (0.7) 0/3 (0) 0/1 (0) 0/1 (0) - - 0 0 0 Chloramphenicol 50/139 (36) 2/3 (66.7) 0/1 (0) 0/1 (0) - - 0 0 0 Enrofloxacin 6/173 (3.5) 0/15 (0) 1/18 (5.6) 1/18 (5.6) - - 0/28 (0) 0/12 (0) 0/3 (0) Florfenicol 24/142 (16.9) 2/8 (25) 0/10 (0) 0/10 (0) - - 0/27 (0) 1/12 (8.3) 0/3 (0) Neomycin 33/170 (19.4) 2/10 (20) 0/9 (0) 0/9 (0) - - 1/28 (3.6) 2/11 (18.2) 0/3 (0) Spectinomycin 101/170 (59.4) 2/10 (20) 2/9 (22.2) 2/9 (22.2) - - 9/27 (33.3) 3/12 (25) 1/3 (33.3) Streptomycin 77/139 (55.4) 2/3 (66.7) 1/1 (100) 1/1 (100) - - 1/1 (100) 0 0 Tetracycline 130/173 (75.1) 9/15 (60) 7/18 (38.9) 7/18 (38.9) - - 12/28 (42.9) 10/12 (83.3) 2/3 (66.7) Trimetho/Sulph 54/173 (31.2) 4/15 (26.7) 2/18 (11.1) 2/18 (11.1) - - 5/28 (17.9) 1/12 (8.3) 1/3 (33.3)

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Table A16.14 – Resistance in E. coli from sheep in England & Wales, Northern Ireland and Scotland in 2014

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Pre-weaning Adult Neonatal Post-weaning Adult Neonatal Pre--weaning Adult Amoxi/Clav 23/105 (21.9) 0/12 (0) 1/5 (20) 3/25 (12) - - 3/21 (14.3) 3/4 (75) 2/4 (50) Ampicillin 58/105 (55.2) 4/12 (33.3) 2/5 (40) 17/25 (68) - - 6/21 (28.6) 3/4 (75) 2/4 (50) Apramycin 3/100 (3) 0/11 (0) 0/2 (0) 2/25 (8) - - 0/20 (0) 0/4 (0) 0/4 (0) Cefotaxime 3/89 (3.4) 0/3 (0) - - - - 0 0 0 Ceftazidime 2/89 (2.2) 0/3 (0) - - - - 0 0 0 Chloramphenicol 26/89 (29.2) 0/3 (0) - - - - 0/1 (0) 0 0 Enrofloxacin 1/105 (1) 0/12 (0) 0/5 (0) 4/25 (16) - - 0/21 (0) 0/4 (0) 0/4 (0) Florfenicol 11/93 (11.8) 0/4 (0) 0/2 (0) 4/25 (16) - - 0/21 (0) 1/4 (25) 0/4 (0) Neomycin 7/100 (7) 1/11 (9.1) 0/3 (0) 25/25 (100) - - 2/21 (9.5) 1/4 (25) 1/4 (25) Spectinomycin 45/100 (45) 3/11 (27.3) 1/2 (50) - - - 5/20 (25) 2/4 (50) 0/4 (0) Streptomycin 38/89 (42.7) 1/3 (33.3) 1/1 (100) - - - 0 0 0 Tetracycline 71/105 (67.6) 8/12 (66.7) 3/5 (60) 19/25 (76) - - 12/21 (57.1) 4/4 (100) 2/4 (50) Trimetho/Sulph 24/105 (22.9) 1/12 (8.3) 1/5 (20) 10/25 (40) - - 5/21 (23.8) 1/4 (25) 1/4 (25)

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Table A16.15 – Resistance in E. coli from sheep in England & Wales, Northern Ireland and Scotland in 2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic Neonatal Pre-weaning Adult Neonatal Post--weaning Adult Neonatal Pre--weaning Adult Amoxi/Clav 19/93 (20.4) 0/13 (0) 1/15 (6.7) 3/9 (33) - - 9/37 (24.3) 1/4 (25) 1/7 (14.3) Ampicillin 60/93 (64.5) 8/13 (61.5) 4/15 (26.7) 7/9 (78) - - 17/37 (45.9) 1/4 (25) 1/7 (14.3) Apramycin 0/93 (0) 1/12 (8.3) 0/6 (0) 0/9 (0) - - 1/35 (2.9) 0/4 (0) 0/7 (0) Cefotaxime 2/74 (2.7) 0/6 (0) 0/1 (0) - - - 0 0 0 Ceftazidime 1/74 (1.4) 0/6 (0) 0/1 (0) - - - 0 0 0 Chloramphenicol 14/74 (18.9) 1/6 (16.7) 1/1 (100) - - - 0/1 (0) 0 0 Enrofloxacin 2/93 (2.2) 0/13 (0) 0/15 (0) 0/9 (0) - - 2/37 (5.4) 0/4 (0) 0/7 (0) Florfenicol 10/74 (13.5) 0/7 (0) 1/8 (12.5) 2/9 (22) - - 4/33 (12.1) 1/4 (25) 0/7 (0) Neomycin 20/93 (21.5) 1/12 (8.3) 0/8 (0) 9/9 (100) - - 2/37 (5.4) 1/4 (25) 1/7 (14.3) Spectinomycin 58/93 (62.4) 5/12 (41.7) 2/6 (33.3) - - - 12/35 (34.3) 0/4 (0) 1/7 (14.3) Streptomycin 51/74 (68.9) 3/6 (50) 1/3 (33.3) - - - 1/1 (100) 0 0 Tetracycline 69/93 (74.2) 8/13 (61.5) 5/15 (33.3) 5/9 (56) - - 21/37 (56.8) 1/4 (25) 4/7 (57.1) Trimetho/Sulph 32/93 (34.4) 2/13 (15.4) 1/15 (6.7) 4/9 (44) - - 6/37 (16.2) 1/4 (25) 0/7 (0)

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Annex 17: Clinical surveillance data for Salmonella spp.

Table A17.1: Resistance in all Salmonella from cattle, pigs, sheep, chickens and turkeys (combined) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 297.9/1879 (15.9) 261/1358 (19.2) 281/1594 (17.6) 34/253 (13.4) 29/257 (11.3) 16/218 (7.3) 29/170 (17.1) 45/147 (30.6) 61/167 (36.5) Amoxi/Clav 10/1879 (0.5) 0/1358 (0) 1/1594 (0.1) 11/253 (4.3) 6/257 (2.3) 3/218 (1.4) 7/170 (4.1) 15/147 (10.2) 17/167 (10.2) Apramycin 34/1879 (1.8) 30/1358 (2.2) 59/1594 (3.7) 3/253 (1.2) 3/257 (1.2) 2/218 (0.9) 0/168 (0) 9/146 (6.2) 10/164 (6.1) Cefotaxime 1/1879 (0.1) 0/1358 (0) 1/1594 (0.1) 0/253 (0) 0/257 (0) 0/218 (0) 0 0 0 Ceftazidime 1/1879 (0.1) 0/1358 (0) 1/1594 (0.1) 0/253 (0) 0/257 (0) 0/218 (0) 0 0 0 Ciprofloxacin 29/1879 (1.5) 19/1358 (1.4) 20/1594 (1.3) 0/253 (0) 0/257 (0) 0/218 (0) 0 0 0 Chloramphenicol 89/1879 (4.7) 107/1358 (7.9) 95/1594 (6) 20/253 (7.9) 10/257 (3.9) 6/218 (2.8) 1/1 (100) 0 0 Gentamicin 48/1879 (2.6) 34/1358 (2.5) 67/1594 (4.2) 2/253 (0.8) 3/257 (1.2) 2/218 (0.9) 0/1 (0) 0 0 Furazolidone 26/1879 (1.4) 10/1358 (0.7) 11/1594 (0.7) 1/253 (0.4) 0/257 (0) 0/218 (0) 0 0 0 Nalidixic Acid 127/1879 (6.8) 58/1358 (4.3) 98/1594 (6.1) 9/253 (3.6) 6/257 (2.3) 12/218 (5.5) 8/165 (4.8) 4/144 (2.8) 4/164 (2.4) Neomycin 31/1879 (1.6) 18/1358 (1.3) 54/1594 (3.4) - - - 0/170 (0) 1/147 (0.7) 1/167 (0.6) Streptomycin 424/1879 (22.6) 351/1358 (25.8) 475/1594 (29.8) 45/253 (17.8) 57/257 (22.2) 37/218 (17) 0 0 0 Sulph Compounds 511/1879 (27.2) 379/1358 (27.9) 525/1594 (32.9) 38/253 (15) 28/257 (10.9) 25/218 (11.5) 0 0 0 Tetracycline 490/1879 (26.1) 350/1358 (25.8) 474/1594 (29.7) 38/253 (15) 26/257 (10.1) 17/218 (7.8) 38/168 (22.6) 65/147 (44.2) 77/167 (46.1) Trim/Sulpho 222/1879 (11.8) 162/1358 (11.9) 199/1594 (12.5) - - - 6/170 (3.5) 26/147 (17.7) 26/167 (15.6)

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Table A17.2: Resistance in all Salmonella from cattle (all ages) from surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 25.9/518 (5) 32/427 (7.5) 23/346 (6.6) 16/153 (10.5) 3/115 (2.6) 2/81 (2.5) 10/105 (9.5) 3/59 (5.1) 12/73 (16.4) Amoxi/Clav 0/518 (0) 0/427 (0) 0/346 (0) 3/153 (2) 1/115 (0.9) 1/81 (1.2) 4/105 (3.8) 3/59 (5.1) 11/73 (15.1) Apramycin 0/518 (0) 0/427 (0) 0/346 (0) 1/153 (0.7) 0/115 (0) 0/81 (0) 0/105 (0) 0/59 (0) 0/73 (0) Cefotaxime 0/518 (0) 0/427 (0) 0/346 (0) 0/153 (0) 0/115 (0) 0/81 (0) 0 0 0 Ceftazidime 0/518 (0) 0/427 (0) 0/346 (0) 0/153 (0) 0/115 (0) 0/81 (0) 0 0 0 Ciprofloxacin 0/518 (0) 0/427 (0) 1/346 (0.3) 0/153 (0) 0/115 (0) 0/81 (0) 0 0 0 Chloramphenicol 5/518 (1) 12/427 (2.8) 10/346 (2.9) 8/153 (5.2) 1/115 (0.9) 0/81 (0) 1/1 (100) 0 0 Gentamicin 1/518 (0.2) 0/427 (0) 0/346 (0) 0/153 (0) 0/115 (0) 0/81 (0) 0/1 (0) 0 0 Furazolidone 0/518 (0) 2/427 (0.5) 0/346 (0) 1/153 (0.7) 0/115 (0) 0/81 (0) 0 0 0 Nalidixic Acid 7/518 (1.4) 0/427 (0) 6/346 (1.7) 4/153 (2.6) 2/115 (1.7) 4/81 (4.9) 7/103 (6.8) 1/59 (1.7) 4/73 (5.5) Neomycin 1/518 (0.2) 1/427 (0.2) 7/346 (2) - - - 0/105 (0) 0/59 (0) 0/73 (0) Streptomycin 32/518 (6.2) 35/427 (8.2) 20/346 (5.8) 23/153 (15) 15/115 (13) 8/81 (9.9) 0 0 0 Sulph Compounds 28/518 (5.4) 33/427 (7.7) 18/346 (5.2) 16/153 (10.5) 3/115 (2.6) 2/81 (2.5) 0 0 0 Tetracycline 32/518 (6.2) 35/427 (8.2) 21/346 (6.1) 16/153 (10.5) 3/115 (2.6) 2/81 (2.5) 12/105 (11.4) 9/59 (15.3) 13/73 (17.8) Trim/Sulpho 4/518 (0.8) 9/427 (2.1) 0/346 (0) - - - 0/105 (0) 0/59 (0) 12/73 (0)

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Table A17.3: Resistance in all Salmonella from pigs (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 132/178 (74.2) 139/204 (68.1) 146/172 (84.9) 12/15 (80) 11/11 (100) 9/14 (64.3) 0 3/3 (100) 6/10 (60) Amoxi/Clav 10/178 (5.6) 0/204 (0) 1/172 (0.6) 4/15 (26.7) 1/11 (9.1) 2/14 (14.3) 0 0/3 (0) 0/10 (0) Apramycin 14/178 (7.9) 18/204 (8.8) 44/172 (25.6) 2/15 (13.3) 1/11 (9.1) 2/14 (14.3) 0 0/3 (0) 2/10 (10) Cefotaxime 1/178 (0.6) 0/204 (0) 1/172 (0.6) 0/15 (0) 0/11 (0) 0/14 (0) 0 0 0 Ceftazidime 1/178 (0.6) 0/204 (0) 1/172 (0.6) 0/15 (0) 0/11 (0) 0/14 (0) 0 0 0 Ciprofloxacin 0/178 (0) 0/204 (0) 0/172 (0) 0/15 (0) 0/11 (0) 0/14 (0) 0 0 0 Chloramphenicol 50/178 (28.1) 75/204 (36.8) 73/172 (42.4) 4/15 (26.7) 4/11 (36.4) 5/14 (35.7) 0 0 0 Gentamicin 15/178 (8.4) 18/204 (8.8) 48/172 (27.9) 1/15 (6.7) 1/11 (9.1) 2/14 (14.3) 0 0 0 Furazolidone 0/178 (0) 1/204 (0.5) 0/172 (0) 0/15 (0) 0/11 (0) 0/14 (0) 0 0 0 Nalidixic Acid 3/178 (1.7) 2/204 (1) 1/172 (0.6) 1/15 (6.7) 1/11 (9.1) 2/14 (14.3) 0 0/3 (0) 0/10 (0) Neomycin 5/178 (2.8) 8/204 (3.9) 12/172 (7) - - - 0 0/3 (0) 1/10 (10) Streptomycin 133/178 (74.7) 140/204 (68.6) 155/172 (90.1) 11/15 (73.3) 11/11 (100) 11/14 (78.6) 0 0 0 Sulph Compounds 150/178 (84.3) 152/204 (74.5) 156/172 (90.7) 11/15 (73.3) 11/11 (100) 11/14 (78.6) 0 0 0 Tetracycline 141/178 (79.2) 152/204 (74.5) 142/172 (82.6) 11/15 (73.3) 11/11 (100) 10/14 (71.4) 0 3/3 (100) 10/10 (100) Trim/Sulpho 99/178 (55.6) 94/204 (46.1) 83/172 (48.3) - - - 0 1/3 (33.3) 1/10 (10)

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Table A17.4: Resistance in all Salmonella from sheep (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 2/91 (2.2) 0/59 (0) 4/57 (7) 1/26 (3.8) 0/12 (0) 0/17 (0) 0/34 (0) 3/26 (11.5) 1/24 (4.2) Amoxi/Clav 0/91 (0) 0/59 (0) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0/34 (0) 3/26 (11.5) 0/24 (0) Apramycin 0/91 (0) 0/59 (0) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0/32 (0) 1/25 (4) 0/22 (0) Cefotaxime 0/91 (0) 0/59 (0) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0 0 0 Ceftazidime 0/91 (0) 0/59 (0) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0 0 0 Ciprofloxacin 0/91 (0) 0/59 (0) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0 0 0 Chloramphenicol 0/91 (0) 0/59 (0) 0/57 (0) 1/26 (3.8) 0/12 (0) 0/17 (0) 0 0 0 Gentamicin 1/91 (1.1) 1/59 (1.7) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0 0 0 Furazolidone 0/91 (0) 0/59 (0) 0/57 (0) 0/26 (0) 0/12 (0) 0/17 (0) 0 0 0 Nalidixic Acid 0/91 (0) 0/59 (0) 0/57 (0) 1/26 (3.8) 0/12 (0) 1/17 (5.9) 1/32 (3.1) 1/25 (4) 0/22 (0) Neomycin 0/91 (0) 0/59 (0) 0/57 (0) - - - 0/34 (0) 0/26 (0) 0/24 (0) Streptomycin 2/91 (2.2) 1/59 (1.7) 5/57 (8.8) 1/26 (3.8) 0/12 (0) 2/17 (11.8) 0 0 0 Sulph Compounds 2/91 (2.2) 1/59 (1.7) 4/57 (7) 1/26 (3.8) 0/12 (0) 2/17 (11.8) 0 0 0 Tetracycline 2/91 (2.2) 1/59 (1.7) 4/57 (7) 0/26 (0) 0/12 (0) 1/17 (5.9) 4/34 (11.8) 4/26 (15.4) 3/24 (12.5) Trim/Sulpho 0/91 (0) 0/59 (0) 1/57 (1.8) - - - 0/34 (0) 0/26 (0) 0/24 (0)

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Table A17.5: Resistance in all Salmonella from chickens (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 63/850 (7.4) 32/525 (6.1) 73/768 (9.5) 16/48 (33.3) 14/106 (13.2) 5/104 (4.8) 0/1 (0) 0/1 (0) 0 Amoxi/Clav 0/850 (0) 0/525 (0) 0/768 (0) 3/48 (6.3) 4/106 (3.8) 0/104 (0) 0/1 (0) 0/1 (0) 0 Apramycin 20/850 (2.4) 12/525 (2.3) 14/768 (1.8) 1/48 (2.1) 2/106 (1.9) 0/104 (0) 0/1 (0) 0/1 (0) 0 Cefotaxime 0/850 (0) 0/525 (0) 0/768 (0) 0/48 (0) 0/106 (0) 0/104 (0) 0 0 0 Ceftazidime 0/850 (0) 0/525 (0) 0/768 (0) 0/48 (0) 0/106 (0) 0/104 (0) 0 0 0 Ciprofloxacin 12/850 (1.4) 3/525 (0.6) 5/768 (0.7) 0/48 (0) 0/106 (0) 0/104 (0) 0 0 0 Chloramphenicol 33/850 (3.9) 19/525 (3.6) 8/768 (1) 8/48 (16.7) 5/106 (4.7) 1/104 (1) 0 0 0 Gentamicin 30/850 (3.5) 15/525 (2.9) 18/768 (2.3) 0/48 (0) 2/106 (1.9) 0/104 (0) 0 0 0 Furazolidone 24/850 (2.8) 7/525 (1.3) 11/768 (1.4) 1/48 (2.1) 0/106 (0) 0/104 (0) 0 0 0 Nalidixic Acid 68/850 (8) 30/525 (5.7) 51/768 (6.6) 4/48 (8.3) 3/106 (2.8) 5/104 (4.8) 0 0 0 Neomycin 24/850 (2.8) 9/525 (1.7) 28/768 (3.6) -/- (-) -/- (-) -/- (-) 0/1 (0) 0/1 (0) 0 Streptomycin 93/850 (10.9) 82/525 (15.6) 117/768 (15.2) 23/48 (47.9) 31/106 (29.2) 16/104 (15.4) 0 0 0 Sulph Compounds 185/850 (21.8) 101/525 (19.2) 158/768 (20.6) 16/48 (33.3) 14/106 (13.2) 10/104 (9.6) 0 0 0 Tetracycline 178/850 (20.9) 76/525 (14.5) 123/768 (16) 16/48 (33.3) 11/106 (10.4) 4/104 (3.8) 0/1 (0) 0/1 (0) 0 Trim/Sulpho 93/850 (10.9) 49/525 (9.3) 100/768 (13) -/- (-) -/- (-) -/- (-) 0/1 (0) 0/1 (0) 0

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Table A17.6: Resistance in all Salmonella from turkeys (all ages) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 75/242 (31) 58/143 (40.6) 35/251 (13.9) - - - 0/7 (0) 1/6 (16.7) 0/1 (0) Amoxi/Clav 0/242 (0) 0/143 (0) 0/251 (0) - - - 0/7 (0) 0/6 (0) 0/1 (0) Apramycin 0/242 (0) 0/143 (0) 1/251 (0.4) - - - 0/7 (0) 0/6 (0) 0/1 (0) Cefotaxime 0/242 (0) 0/143 (0) 0/251 (0) - - - 0/7 (0) 0/6 (0) 0/1 (0) Ceftazidime 0/242 (0) 0/143 (0) 0/251 (0) - - - 0/7 (0) 0/6 (0) 0/1 (0) Ciprofloxacin 17/242 (7) 16/143 (11.2) 14/251 (5.6) - - - 0/7 (0) 0/6 (0) 0/1 (0) Chloramphenicol 1/242 (0.4) 1/143 (0.7) 4/251 (1.6) - - - 0/7 (0) 0/6 (0) 0/1 (0) Gentamicin 1/242 (0.4) 0/143 (0) 1/251 (0.4) - - - 0/7 (0) 0/6 (0) 0/1 (0) Furazolidone 2/242 (0.8) 0/143 (0) 0/251 (0) - - - 0/7 (0) 0/6 (0) 0/1 (0) Nalidixic Acid 49/242 (20.2) 26/143 (18.2) 40/251 (15.9) - - - 0/7 (0) 0/6 (0) 0/1 (0) Neomycin 1/242 (0.4) 0/143 (0) 7/251 (2.8) ------Streptomycin 164/242 (67.8) 93/143 (65) 178/251 (70.9) - - - 0/7 (0) 0/6 (0) 0/1 (0) Sulph Compounds 146/242 (60.3) 92/143 (64.3) 189/251 (75.3) - - - 0/7 (0) 0/6 (0) 0/1 (0) Tetracycline 137/242 (56.6) 86/143 (60.1) 184/251 (73.3) - - - 0/7 (0) 1/6 (16.7) 0/1 (0) Trim/Sulpho 26/242 (10.7) 10/143 (7) 15/251 (6) ------

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Table A17.7: Resistance in all Salmonella Dublin from cattle, pigs, sheep, chickens and turkeys (combined) from clinical surveillance in England and Wales, Northern Ireland and Scotland, 2013-2015

No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 1/393 (0.3) 2/286 (0.7) 4/226 (1.8) 9/134 (6.7) 12/110 (10.9) 6/79 (7.6) 0 0 0 Chloramphenicol 0/393 (0) 0/286 (0) 1/226 (0.4) 0/134 (0) 0/110 (0) 0/79 (0) 1/1 (100) 0 0 Furazolidone 0/393 (0) 1/286 (0.3) 0/226 (0) 0/134 (0) 1/110 (0.9) 0/79 (0) 0 0 0 Nalidixic Acid 4/393 (1) 0/286 (0) 5/226 (2.2) 1/134 (0.7) 0/110 (0) 0/79 (0) 2/77 (2.6) 4/52 (7.7) 1/56 (1.8) Neomycin 1/393 (0.3) 1/286 (0.3) 5/226 (2.2) - - - 0/77 (0) 0/52 (0) 0/56 (0) Streptomycin 5/393 (1.3) 7/286 (2.4) 9/226 (4) 0/134 (0) 0/110 (0) 0/79 (0) 0/77 (0) 0/52 (0) 0/56 (0) Sulpha/Trim 0/393 (0) 2/286 (0.7) 0/226 (0) 1/134 (0.7) 0/110 (0) 0/79 (0) 0 0 0 Sulph Compounds 0/393 (0) 2/286 (0.7) 0/226 (0) - - - 0/77 (0) 0/52 (0) 0/56 (0) Tetracycline 0/393 (0) 1/286 (0.3) 1/226 (0.4) 2/134 (1.5) 2/110 (1.8) 5/79 (6.3) 1/75 (1.3) 0/52 (0) 0/56 (0)

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No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 95/165 (57.6) 97/224 (43.3) 77/165 (46.7) 29/36 (80.6) 19/28 (67.9) 13/24 (54.2) 0 0 0 Chloramphenicol 3/165 (1.8) 2/224 (0.9) 0/165 (0) 20/36 (55.6) 10/28 (35.7) 6/24 (25) 0 0 0 Furazolidone 58/165 (35.2) 82/224 (36.6) 75.9/165 (46) 31/36 (86.1) 19/28 (67.9) 14/24 (58.3) 0 0 0 Nalidixic Acid 0/165 (0) 0/224 (0) 0/165 (0) 29/36 (80.6) 19/28 (67.9) 12/24 (50) 10/11 (90.9) 10/10 (100) 21/22 (95.5) Neomycin 7.92/165 (4.8) 2/224 (0.9) 2/165 (1.2) - - - 0/11 (0) 0/10 (0) 1/22 (4.5) Streptomycin 1/165 (0.6) 0/224 (0) 4/165 (2.4) 31/36 (86.1) 10/28 (35.7) 13/24 (54.2) 10/11 (90.9) 9/10 (90) 17/22 (77.3) Sulpha/Trim 90/165 (54.5) 89/224 (39.7) 85/165 (51.5) 0/36 (0) 0/28 (0) 0/24 (0) 0 0 0 Sulph Compounds 74/165 (44.8) 80/224 (35.7) 53/165 (32.1) - - - 0/11 (0) 1/10 (10) 1/22 (4.5) Tetracycline 100/165 (60.6) 98/224 (43.8) 80/165 (48.5) 4/36 (11.1) 1/28 (3.6) 2/24 (8.3) 4/11 (36.4) 1/10 (10) 4/22 (18.2)

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No. resistant / No. tested (Percentage resistant) England & Wales Northern Ireland Scotland Antibiotic 2013 2014 2015 2013 2014 2015 2013 2014 2015 Ampicillin 286/2328 (12.3) 233/1837 (12.7) 292/2198 (13.3) 29/36 (80.6) 19/28 (67.9) 13/24 (54.2) 0 0 0 Chloramphenicol 33/2328 (1.4) 29/1837 (1.6) 64/2198 (2.9) 20/36 (55.6) 10/28 (35.7) 6/24 (25) 0 0 0 Furazolidone 40/2328 (1.7) 33/1837 (1.8) 53/2198 (2.4) 31/36 (86.1) 19/28 (67.9) 14/24 (58.3) 0 0 0 Nalidixic Acid 72/2328 (3.1) 39/1837 (2.1) 42/2198 (1.9) 29/36 (80.6) 19/28 (67.9) 12/24 (50) 26/80 (32.5) 51/85 (60) 55/89 (61.8) Neomycin 133/2328 (5.7) 73/1837 (4) 121/2198 (5.5) - - - 0/82 (0) 1/85 (1.2) 0/89 (0) Streptomycin 79/2328 (3.4) 37/1837 (2) 70/2198 (3.2) 31/36 (86.1) 10/28 (35.7) 13/24 (54.2) 19/82 (23.2) 36/85 (42.4) 44/89 (49.4) Sulpha/Trim 447/2328 (19.2) 345/1837 (18.8) 497/2198 (22.6) 0/36 (0) 0/28 (0) 0/24 (0) 0 0 0 Sulph Compounds 284/2328 (12.2) 384/1837 (20.9) 229/2198 (10.4) - - - 6/82 (7.3) 25/85 (29.4) 25/89 (28.1) Tetracycline 617/2328 (26.5) 384/1837 (20.9) 580/2198 (26.4) 4/36 (11.1) 1/28 (3.6) 2/24 (8.3) 3/79 (3.8) 3/82 (3.7) 0/86 (0)

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Table A17.10: Top ten Salmonella serovars isolated in Northern Ireland between 2013-2015

Rank 2013 2014 2015 1 Dublin / (458 isolations) Dublin / (321 isolations) Derby / (437 isolations) 2 Mbandaka / (278 isolations) Mbandaka / (196 isolations) Mbandaka / (335 isolations) 3 Montevideo / (248 isolations) Kedougou / (128 isolations) Dublin / (247 isolations) 4 Senftenberg / (205 isolations) Senftenberg / (122 isolations) Kedougou / (230 isolations) 5 Kedougou / (192 isolations) Montevideo / (115 isolations) 13,23:i:- / (189 isolations) 6 Derby (176 isolations) 13,23:i:- / (107 isolations) Senftenberg / (90 isolations) 7 13,23:i:- / (134 isolations) Typhimurium / (105 isolations) Enteritidis / (87 isolations) 8 Typhimurium / (87 isolations) 4,5,12:i:- / (71 isolations) Typhimurium / (67 isolations) 9 Ohio / (65 isolations) Derby / (54 isolations) 4,12:i:- / (58 isolations) 10 Newport / (59 isolations) Newport / (44 isolations) 4,5,12:i:- / (54 isolations)

Table A17.11: Top ten Salmonella serovars isolated in Scotland between 2013-2015

Rank 2013 2014 2015 1 Dublin / (80 isolations) Dublin / (58 isolations) Dublin / (64 isolations) 2 Typhimurium / (34 isolations) Typhimurium / (53 isolations) Typhimurium / (49 isolations) 3 Arizonae / (23 isolations) Arizonae / (16 isolations) Arizonae / (17 isolations) 4 Montevideo / (18 isolations) Montevideo / (8 isolations) Montevideo / (9 isolations) 5 Bovismorbificans / (7 isolations) Enteritidis / (4 isolations) Spp. / (7 isolations) 6 Bovi / (6 isolations) Spp. / (2 isolations) Derby / (2 isolations) 7 Spp. / (4 isolations) Mbandaka / (2 isolations) Enteritidis / (2 isolations) 8 Derby / (2 isolations) Bovismorbificans / (1 isolations) Spp. / (6 isolations) 9 Tennessee / (2 isolations) Group C2 / (1 isolations) Mbandaka / (2 isolations) 10 Senfentenberg / (2 isolations) Aarhus / (1 isolations Senftenberg / (2 isolations)

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Annex 18: Data limitations

Antibiotic sales data are considered to be an overestimate of use

 Sales data do not permit accurate analysis of antibiotic consumption by animal species or production category. Some formulations of antibiotics are authorised with indications for use in more than one species, e.g. pigs and poultry. It is not possible to ascertain from sales data in which species the product was used.  A given quantity of antibiotic may represent many doses in small animals or few doses in large animals. It is not possible to predict the number of doses represented by the quantity sold.  Changes in quantities of veterinary antibiotics sold should be considered in parallel with changes in the UK animal population over the corresponding time period. The populations of animal species are an important denominator and may vary quite markedly from year to year depending on market conditions for livestock derived food. Similarly variations in the size of the animals being treated should be taken into consideration as larger animals will require a larger relative quantity of antibiotics over a treatment period.  To try and address the variation in animal populations and demographics, over time and between countries, the ESVAC project has developed a Population Correction Unit (PCU), a calculation that estimates the weight of the animal (or group of animals) receiving an antibiotic at the most likely time of administration. This unit is now used across EU member states and is currently the best approximation of consumption. We have used this form of analysis in this report.  Sales data in general over estimate use, as not all antibiotics sold will be used. There is natural wastage resulting from pack sizes that do not meet dose need, and from drug expiry.  Some products may be sold to UK feed mills for inclusion in feed which is then exported outside of the UK, currently there is no method for separating these sales from the total UK sales data, resulting in an over estimate of use in UK feed.  Medication sold for use in humans may be used in animals under certain circumstances, according to the prescribing cascade; figures on such use are not included in the data presented. Further information on cascade prescribing can be found in Annex 5.

Population data:

 The food-producing animal population figures presented in this report are based on a single point in time “census”. While these figures can be considered accurately reflective of the total annual cattle population, they are less so for other animal species. The figures are least representative for poultry raised for meat where the total number at any one time only represent a small percentage of the total raised each year. The sheep population also varies significantly pre and post lambing season each year. These factors are taken into consideration when the PCU is calculated (see Annex 2).

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Resistance data, clinical surveillance

There are a number of limitations associated with the antibiotic resistance data and they should be borne in mind when interpreting results from the veterinary clinical surveillance. This is a biased population and cannot be considered to accurately reflect the bacterial populations present within the general animal population in the UK:

 Veterinary surgeons have the option to submit samples to private laboratories rather than Government laboratories/ Veterinary Investigation Centres. The proportion of samples that Government laboratories tests compared to other laboratories is not known, and therefore we cannot know how representative the samples processed by APHA, SACCVS, and AFBI are of total diagnostic submissions.

 Furthermore, geographical proximity of a farm or veterinary practice to a Government diagnostic laboratory may have an impact on the submission rate of samples; clinical surveillance may therefore, naturally, over‐represent the animal populations within certain geographical areas.

 Other factors can also influence the submission rate of samples to veterinary diagnostic laboratories. These can include for example the severity of disease, impact on production or the value of the animals involved.

 The levels of resistance demonstrated by the clinical surveillance isolates presented in this report may be higher than those seen in the wider bacterial populations present within animals in England and Wales. This is because samples from diseased animals may be submitted from animals that have been unresponsive to initial antibiotic therapy, and thus the isolates recovered may have already been exposed to antibiotic pressure(s).

 Isolates from companion animals which are submitted to APHA are only investigated for antibiotic resistance if there is a public health concern, and therefore bacteria from these animal groups are under‐represented in this report. APHA does not provide a veterinary diagnostic service for companion animals.

 The veterinary clinical surveillance data detail the number of bacterial isolates that underwent sensitivity testing, but not the numbers of animals for which samples were submitted for examination. Several bacteria may have been cultured from an individual animal or from a group of animals on the same farm. This type of clustering is not accounted for in the report, though since only low numbers of bacteria are usually subjected to susceptibility testing from the same outbreak of disease, its importance is probably limited.

 The diagnostic tests performed on any sample received through the clinical surveillance programme are dependent on the individual case; i.e. isolates of the same bacterial species are not always tested against the same panel of antibiotics. Therefore, if resistance is not detected in one isolate, it may not mean that resistance is not present, just that it was not tested for. This is especially true of commensal organisms.

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 The breakpoints used for determining resistance for isolates recovered under the veterinary clinical surveillance programme in GB are those as recommended by BSAC. These breakpoints were originally determined for human medicine and their use in veterinary medicine is based on the assumption that the concentration of antibiotic at the site of infection is approximately the same in animals as it is in humans. Currently it is not known if this assumption is always correct, especially as different dosing regimens may be used in different animals and pharmacokinetics may vary between species. Currently, there is insufficient data available to apply animal species specific breakpoints to all organism/antibiotic combinations where these are required.

 Different antibiotic susceptibility testing methodologies are used in England & Wales (APHA), Scotland (SACCVS), and Northern Ireland (AFBI). APHA and SACCVS use BSAC methodology to determine resistance/susceptibility based on human clinical breakpoints, whilst AFBI use CLSI. In light of the different methodologies and breakpoints used, the amalgamated results of UK wide monitoring should be interpreted with caution.

 For AST testing done by APHA, in the case of some veterinary drug/bug combinations a BSAC cut‐off may not exist. In this case, APHA may have derived a tentative or suggested breakpoint or the historical veterinary breakpoint (zone size cut‐off of resistant <=13mm) may have been used to define resistance. The breakpoints used are set out in Annex x.

 Escherichia coli isolates are not collected from routine samples from healthy livestock in Northern Ireland. Only clinical cases submitted for post-mortem investigation when colibacillosis, or similar diseases, will proceed to isolate pathogenic E. coli. AMR testing on E. coli isolates is mainly performed if samples are coming from <2-week old calves and animals with bovine mastitis.

 With regards to E. coli, each organisation in the United Kingdom sets their own criteria for testing AMR in E. coli from clinically sick animals and these criteria are not uniform. This is pertinent to highlight as the selection of isolates for susceptibility testing based on age or other criteria can influence the result obtained. Bacterial isolates recovered from young animals can often be more resistant than those from older animals and this relates to the fact that antimicrobials are in general more frequently administered to young animals than to older animals.

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Annex 19: Data sources

Marketing Authorisation Holders (MAHs) It is mandatory for Market Authorisation Holders of manufactured antibiotics to provide the Veterinary Medicines Directorate with total annual sales data for each antibiotic product sold within the UK. Data are collected, verified and analysed to calculate the total weight, in tonnes, of each active ingredient sold for each antibiotic. Antibiotic sales data are collected as a proxy for antibiotic use.

Periodic Safety Update Reports (PSURs) Sales figures submitted by MAHs in PSURs for the purpose of Pharmacovigilance, were used to validate sales figures published in this report. Where a PSUR had been returned to the VMD Pharmacovigilance team in the 2015 calendar year reported sales were compared to those returned to the AMR team and any discrepancies were queried.

To calculate the Population Correction Unit, data are supplied by:

Defra Statistics division The live weight of animals slaughtered for food are calculated by Defra. The population numbers of food producing animals are supplied by Defra via the Agriculture in the UK report.

CEFAS The annual live weight of fish at slaughter for the UK is supplied by CEFAS (Centre for Environment, Fisheries and Aquaculture Science).

TRACES Import and export figures obtained from TRACES are provided by European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) and used in the calculation of the PCU.

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Annex 20: Glossary of Terms

a.i. Active Ingredient; the part of an antibiotic medicine that acts against the bacterial infection.

AHDB Animal Health and Development Board

Aminoglycosides A closely related group of bactericidal antibiotics derived from bacteria of the order Actinomycetales. Polycationic compounds that contain an aminocyclitol with cyclic amino-sugars attached by glycoside linkages. Sulphate salts are generally used. They have broadly similar toxicological features.

Antibiotic A term synonymous with antibacterials.

Antimicrobial A general term for any compound with a direct action on micro- organisms used for treatment or prevention of infections. Antimicrobials include antibacterials (antibiotics), antivirals, antifungals and antiprotozoals.

Antimicrobial The ability of a micro-organism to grow or survive in the presence of Resistance an antimicrobial that is usually sufficient to inhibit or kill micro- organisms of the same species.

-Lactam Semi-synthetic antibiotics derived from penicillin G or cephalosporin C, natural antibiotics produced by the mould Cephalosporium acremonium. Bactericidal products that act by inhibiting synthesis of the bacterial cell wall.

BPC British Poultry Council

CBP Clinical Break Point

CHAWG Cattle Health and Welfare Group

Critically Important These are antibiotics which; are the sole or one of few available Antibiotics treatments for serious human disease; and are used to treat diseases caused by organisms that may be transmitted to humans from non-human sources or, human diseases caused by organisms that may acquire resistance genes from non-human sources, (WHO definition). They include the following classes of antibiotics; fluoroquinolones; 3rd and 4th generation cephalosporins; and macrolides. HP-CIA Highest Priority Critically Important Antibiotics

Defra Department for Environment, Food and Rural Affairs

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ECDC European Centre for Disease Prevention and Control

ECV Epidemiological cut-off value

EFSA European Food Safety Authority

EMA European Medicines Agency

Eurostat Eurostat is the statistical office of the European Union.

ESVAC European Surveillance of Veterinary Antimicrobial Consumption

FAO Food and Agriculture Organisation of the United Nations.

Fluoroquinolone A sub-group of the quinolone compounds, having the addition of a fluorine atom and the 7-piperazinyl group. Broad-spectrum antibacterials with properties more suited to the treatment of systemic infections.

Food Animals Animals used for food production including: cattle, sheep, pigs, poultry, salmon, trout and bees.

Injectable Product A product which is administered to animals via injection.

Intramammary A product which is administered into the udder. Product Macrolide A large group of antibiotics mainly derived from Streptomyces spp. Weak bases that are only slightly soluble in water. They have low toxicity and similar antibiotic activity with cross-resistance between individual members of the group. Thought to act by interfering with bacterial protein synthesis.

Medicated Feeding Feeding stuffs that contain a veterinary medicine and that are stuff intended for feeding to animals without further processing.

Metaphylaxis The treatment of a group of animals where one or more individuals within the group has received a clinical diagnosis.

Non-Food Animals Animals not reared for food. These are mainly companion animals including, dogs, cats, horses, small mammals, rabbits and birds.

OIE World Organisation for Animal Health

PHWC Pig Health and Welfare Council

Population This is a technical unit of measurement which is used to represent Correction Unit the estimated weight at treatment of livestock and slaughtered

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(PCU) animals. 1 PCU = 1 kg of different categories of livestock and slaughtered animals.

Sulphonamide A group of bacteriostatic compounds that interfere with folic acid synthesis of susceptible organisms. They all have similar antibiotic activity but different pharmacokinetic properties.

Tetracycline A group of antibiotics derived from Streptomyces spp. They are usually bacteriostatic at concentrations achieved in the body and act by interfering with protein synthesis in susceptible organisms. All have a broad spectrum of activity.

TRACES European Commission’s Director General Health and Consumer owned - The 'TRAde Control and Expert System' (TRACES) is a management tool for tracking the movements of animals, products of animal and non-animal origin and since version 6.00 also of plants, from both outside the European Union and within its territory.

Trimethoprim Compounds with a similar action to sulphonamides, acting by interfering with folic acid synthesis, but at a different stage in the metabolic pathway. Display a similar spectrum of activity to, and are often used in combination with, sulphonamides.

VMD Veterinary Medicines Directorate, an Executive Agency of the Department for Environment, Food and Rural Affairs (Defra).

Water/Oral Product A product that is administered to animals orally. Includes tablets, boluses, capsules, dissolvable powders and sachets, solutions, etc.

WHO World Health Organisation

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Annex 21: Contributors

Compiled by:

The Veterinary Medicines Directorate Woodham Lane New Haw Surrey, KT15 3LS

Contributing Pharmaceutical Companies and Other Marketing Authorisation Holders

 Alfasan Nederland BV  Kernfarm B.V.  Animalcare Limited  Krka Dd  aniMedica GmbH  Laboratorios Calier S.A.  Avimedical  Laboratorios Hipra S.A.  Bayer Plc  Laboratorios Karizoo S.A.  Bimeda Chemicals Ltd  Laboratorios Maymo S.A.  Boehringer Ingelheim Ltd  Laboratorios SYVA S.A.U  Ceva Animal Health Ltd  Laboratorios Velvian, S.L.  Chanelle Animal Health Ltd  Lavet Pharmaceuticals Ltd  Continental Farmaceutica SL.  Le Vet B.V.  CP Pharma Handelsgesellschaft mbH  Listow Limited  Cross Vetpharm Group Ltd  Merial Animal Health Ltd  Dechra Ltd  Miklich Laboratorios S.L  Divasa Farmavic S.A.  Nimrod Veterinary Products Ltd  Dopharma Research B.V.  Norbrook Laboratories Ltd  ECO Animal Health  Novartis Animal Health UK Ltd  Ecuphar N.V.  Oropharma N.V.  Eli Lilly & Company Ltd  Pharmaq Ltd  Emdoka bvba  Phibro Animal Health SA  Eurovet Animal Health B.V.  Qalian Ltd  Fatro S.P.A.  Richter Pharma  Forte Healthcare Ltd  Sogeval S.A.  Forum Products Limited  SP Veterinaria, S.A.  Franklin Pharmaceuticals Ltd  Triveritas Ltd  Global Vet Health S.L  Universal Farma S.L  Harkers Ltd  Univet Ltd  Huvepharma N.V.  Vétoquinol UK Ltd  I.C.F. Sri Industria Chimica Fine  Vetpharma Animal Health S.L  Industrial Veterinaria S.A.  Virbac S.A  Intervet UK Ltd  VMD NV  Kela N.V.

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Contributors of other statistics:

 Defra Statistics Branch Scottish Government  Department of Agriculture and Rural Development, Northern Ireland  Centre for Environment Fisheries and Aquaculture Science

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